Saccharomyces boulardii for the prevention of antibiotic-associated diarrhea in adult hospitalized patients: a single-center, randomized, double-blind, placebo-controlled trial. Effect of Lactobacillus F19 on the emergence of antibiotic-resistant microorganisms in the intestinal microflora. The effect of a multispecies probiotic on the intestinal microbiota and bowel movements in healthy volunteers taking the antibiotic amoxycillin. Lack of effect of Lactobacillus GG on antibiotic-associated diarrhea: a randomized, placebo-controlled trial. Use of probiotic Lactobacillus preparation to prevent diarrhoea associated with antibiotics: randomised double blind placebo controlled trial. Lactobacillus plantarum 299v reduces colonisation of Clostridium difficile in critically ill patients treated with antibiotics. [Effect of probiotic Saccharomyces boulardii on prevention of antibiotic-associated diarrhea in adult outpatients with amoxicillin treatment]. Prevention of antibiotic-associated diarrhoea by a fermented probiotic milk drink. Prophylactic Saccharomyces boulardii in the prevention of antibiotic-associated diarrhea: a prospective study. Intake of Lactobacillus plantarum reduces certain gastrointestinal symptoms during treatment with antibiotics. Efficacy of BIO K+ CL1285 in the reduction of antibiotic-associated diarrhea - a placebo controlled double-blind randomized, multi-center study. Clinical trial: effectiveness of Lactobacillus rhamnosus (strains E/N, Oxy and Pen) in the prevention of antibiotic-associated diarrhoea in children. Efficacy and safety of Saccharomyces boulardii in prevention of antibiotic-associated diarrhoea due to Helicobacterpylori eradication. Prophylactic Lactobacillus GG reduces antibiotic-associated diarrhea in children with respiratory infections: a randomized study. Prevention of antibiotic-associated diarrhea by Saccharomyces boulardii: a prospective study. Efficacy and safety of Saccharomyces boulardii in the 14-day triple anti-Helicobacter pylori therapy: a prospective randomized placebo-controlled double-blind study. Prevention of beta-lactam-associated diarrhea by Saccharomyces boulardii compared with placebo. Effect of a fermented milk combining Lactobacillus acidophilus Cl1285 and Lactobacillus casei in the prevention of antibiotic-associated diarrhea: a randomized, double-blind, placebo-controlled trial. Effect of Lactobacillus GG yoghurt in prevention of antibiotic associated diarrhoea. Feasibility and tolerability of probiotics for prevention of antibiotic-associated diarrhoea in hospitalized US military veterans. The lack of therapeutic effect of Saccharomyces boulardii in the prevention of antibiotic-related diarrhoea in elderly patients. Oral supplementation with lactic acid-producing bacteria during intake of clindamycin. Clostridium difficile pilot study: effects of probiotic supplementation on the incidence of C. difficile diarrhoea. Dose-response efficacy of a proprietary probiotic formula of Lactobacillus acidophilus CL1285 and Lactobacillus casei LBC80R for antibiotic-associated diarrhea and Clostridium difficile-associated diarrhea prophylaxis in adult patients. Efficacy of Clostridium butyricum preparation concomitantly with Helicobacter pylori eradication therapy in relation to changes in the intestinal microbiota. Effect of Clostridium butyricum on fecal flora in Helicobacter pylori eradication therapy. Saccharomyces boulardii in the prevention of antibiotic-associated diarrhoea in children: a randomized double-blind placebo-controlled trial.
Antibiotic-associated diarrhea (AAD) and Clostridium difficile-associated diarrhea (CDAD) are common complications of antibiotic use. Probiotics were effective in preventing AAD and CDAD in several randomized controlled trials. This study was aimed at testing the effect of Saccharomyces boulardii on the occurrence of AAD and CDAD in hospitalized patients.
                A single-center, randomized, double-blind, placebo-controlled, parallel-group trial was performed. Patients being prescribed antibiotics or on antibiotic therapy for <48 h were eligible. Exclusion criteria were ongoing diarrhea, recent assumption of probiotics, lack of informed consent, inability to ingest capsules, and severe pancreatitis. Patients received a capsule containing S. boulardii or an indistinguishable placebo twice daily within 48 h of beginning antibiotic therapy, continued treatment for 7 days after antibiotic withdrawal, and were followed for 12 weeks after ending antibiotic treatment.
                Of 562 consecutive eligible patients, 275 patients aged 79.2 ± 9.8 years (134 on placebo) were randomized and 204 aged 78.4 ± 10.0 years (98 on placebo) completed the follow-up. AAD developed in 13.3% (13/98) of the patients receiving placebo and in 15.1% (16/106) of those receiving S. boulardii (odds ratio for S. boulardii vs. placebo, 1.16; 95% confidence interval (CI), 0.53-2.56). Five cases of CDAD occurred, 2 in the placebo group (2.0%) and 3 in the probiotic group (2.8%; odds ratio for S. boulardii vs. placebo, 1.40; 95% CI, 0.23-8.55). There was no difference in mortality rates (12.7% vs. 15.6%, P=0.60).
                In elderly hospitalized patients, S. boulardii was not effective in preventing the development of AAD. Probiotic lactic-acid-producing bacteria have been used for prevention of gastrointestinal diseases. The aim of the present study was to examine whether Lactobacillus F19 in conjunction with treatment with penicillin, ciprofloxacin or norfloxacin prevents establishment of resistant bacteria in the gastrointestinal tract.
                Twenty patients admitted to hospital due for treatment with penicillin and 16 patients due for treatment with ciprofloxacin or norfloxacin were included in the study. In either group, the patients were randomized into two groups, receiving placebo or an active probiotic product. Faecal samples were collected before treatment, on day 10 and 1 month after the start of the treatment. Isolates of enterococci, enterobacteria and Bacteroides fragilis species were screened for resistance to penicillin and ciprofloxacin, respectively.
                Administration of penicillin did not influence resistance in enterococci while quinolone resistance increased during quinolone treatment. Susceptibility to ampicillin and piperacillin/tazobactam decreased in enterobacteria during penicillin treatment and ciprofloxacin resistance increased in the quinolone group. Penicillin and quinolones did not influence the resistance rates of Bacteroides isolates. No major differences were observed between the probiotic- and placebo-supplemented groups.
                There was a limited effect of Lactobacillus F19 on the emergence of resistant isolates during treatment with penicillin and quinolones. One of the side effects of antimicrobial therapy is a disturbance of the intestinal microbiota potentially resulting in antibiotic-associated diarrhea (AAD). In this placebo-controlled double-blind study, the effect of a multispecies probiotic on the composition and metabolic activity of the intestinal microbiota and bowel habits was studied in healthy volunteers taking amoxycillin.
                Forty-one healthy volunteers were given 500 mg amoxycillin twice daily for 7 days and were randomized to either 5 g of a multispecies probiotic, Ecologic AAD (10(9) cfu/g), or placebo, twice daily for 14 days. Feces and questionnaires were collected on day 0, 7, 14, and 63. Feces was analyzed as to the composition of the intestinal microbiota, and beta-glucosidase activity, endotoxin concentration, Clostridium difficile toxin A, short chain fatty acids (SCFAs), and pH were determined. Bowel movements were scored according to the Bristol stool form scale.
                Mean number of enterococci increased significantly from log 4.1 at day 0 to log 5.8 (day 7) and log 6.9 (day 14) cfu/g feces (P < 0.05) during probiotic intake. Although no other significant differences were observed between both intervention groups, within each group significant changes were found over time in both microbial composition and metabolic activity. Moreover, bowel movements with a frequency >or=3 per day for at least 2 days and/or a consistency >or=5 for at least 2 days were reported less frequently in the probiotic compared to the placebo group (48%vs 79%, P < 0.05).
                Apart from an increase in enterococci no significant differences in microbial composition and metabolic activity were observed in the probiotic compared with the placebo group. However, changes over time were present in both groups, which differed significantly between the probiotic and the placebo arm, suggesting that the amoxycillin effect was modulated by probiotic intake. Moreover, the intake of a multispecies probiotic significantly reduced diarrhea-like bowel movements in healthy volunteers receiving amoxycillin. To assess the efficacy of Lactobacillus GG in preventing antibiotic-associated diarrhea (AAD) in adults and, secondarily, to assess the effect of coadministered Lactobacillus GG on the number of tests performed to determine the cause of diarrhea.
                In this prospective, randomized, double-blind, placebo-controlled trial conducted from July 1998 to October 1999, 302 hospitalized patients receiving antibiotics were randomized to receive Lactobacillus GG, 20 x 10(9) CFU/d, or placebo for 14 days. Subjects recorded the number of stools and their consistency daily for 21 days. The primary outcome was the proportion of patients who developed diarrhea in the first 21 days after enrollment. Weekly telephone follow-up was also performed. Results were analyzed in an intention-to-treat fashion.
                Diarrhea developed in 39 (29.3%) of 133 patients randomized to receive Lactobacillus GG and in 40 (29.9%) of 134 patients randomized to receive placebo (P=.93). No additional difference in the rate of occurrence of diarrhea was found between treatment and placebo patients in a subgroup analysis of those treated with beta-lactam vs non-beta-lactam antibiotics. Too few patients had stool cultures, additional laboratory tests for diarrhea, or a positive diagnosis of Clostridium difficile infection to assess between-group differences.
                Lactobacillus GG in a dose of 20 x 10(9) CFU/d did not reduce the rate of occurrence of diarrhea in this sample of 267 adult patients taking antibiotics initially administered in the hospital setting. To determine the efficacy of a probiotic drink containing Lactobacillus for the prevention of any diarrhoea associated with antibiotic use and that caused by Clostridium difficile.
                Randomised double blind placebo controlled study.
                135 hospital patients (mean age 74) taking antibiotics. Exclusions included diarrhoea on admission, bowel pathology that could result in diarrhoea, antibiotic use in the previous four weeks, severe illness, immunosuppression, bowel surgery, artificial heart valves, and history of rheumatic heart disease or infective endocarditis.
                Consumption of a 100 g (97 ml) drink containing Lactobacillus casei, L bulgaricus, and Streptococcus thermophilus twice a day during a course of antibiotics and for one week after the course finished. The placebo group received a longlife sterile milkshake.
                Primary outcome: occurrence of antibiotic associated diarrhoea. Secondary outcome: presence of C difficile toxin and diarrhoea.
                7/57 (12%) of the probiotic group developed diarrhoea associated with antibiotic use compared with 19/56 (34%) in the placebo group (P=0.007). Logistic regression to control for other factors gave an odds ratio 0.25 (95% confidence interval 0.07 to 0.85) for use of the probiotic, with low albumin and sodium also increasing the risk of diarrhoea. The absolute risk reduction was 21.6% (6.6% to 36.6%), and the number needed to treat was 5 (3 to 15). No one in the probiotic group and 9/53 (17%) in the placebo group had diarrhoea caused by C difficile (P=0.001). The absolute risk reduction was 17% (7% to 27%), and the number needed to treat was 6 (4 to 14).
                Consumption of a probiotic drink containing L casei, L bulgaricus, and S thermophilus can reduce the incidence of antibiotic associated diarrhoea and C difficile associated diarrhoea. This has the potential to decrease morbidity, healthcare costs, and mortality if used routinely in patients aged over 50.
                National Research Register N0016106821. The incidence of Clostridium difficile-associated disease (CDAD) in hospitalised patients is increasing. Critically ill patients are often treated with antibiotics and are at a high risk of developing CDAD. Lactobacillus plantarum 299v (Lp299v) has been found to reduce recurrence of CDAD. We investigated intensive care unit (ICU) patients with respect to the impact of Lp299v on C. difficile colonisation and on gut permeability and parameters of inflammation and infection in that context.
                Twenty-two ICU patients were given a fermented oatmeal gruel containing Lp299v, and 22 received an equivalent product without the bacteria. Faecal samples for analyses of C. difficile and Lp299v were taken at inclusion and then twice a week during the ICU stay. Other cultures were performed on clinical indication. Infection and inflammation parameters were analysed daily. Gut permeability was assessed using a sugar probe technique.
                Colonisation with C. difficile was detected in 19% (4/21) of controls but in none of the Lp299v-treated patients (P<0.05).
                Enteral administration of the probiotic bacterium Lp299v to critically ill patients treated with antibiotics reduced colonisation with C. difficile. Antibiotic-associated diarrhea is one of the most common adverse effects of antimicrobials. Any antimicrobial can potentially produce diarrhea but beta-lactamics have a higher risk. Among these, amoxicillin is widely indicated in ambulatory practice. One of the alternatives suggested to prevent antibiotic-associated diarrhea, is the use of the probiotic Saccharomyces boulardii.
                To evaluate whether the concomitant use of Saccharomyces boulardii and amoxicillin can prevent antibiotic associated diarrhea in ambulatory adults with acute infections diseases, without provoking other adverse effects.
                Eighty six adults (aged 15 to 81 years) with acute infectious diseases, excluding those arising in the gastrointestinal tract, that received a prescription of oral amoxicillin for 5 to 10 days, were included. In a controlled randomized, double blind trial, 41 patients were assigned to receive lyophilized Saccharomyces boulardii (500 mg/day) during 12 days, and 45 patients were assigned to placebo for the same period.
                Ten percent of patients (9/86) reported acute diarrhea, 9,8% (4/41) in the experimental group and 11.196 (5/45) in the control group (p = 100). No adverse effects were associated to the use of the probiotic.
                Saccharomyces boulardii (500 mg/day) did not prevent diarrhea related to amoxicillin. To study the preventive effect of a milk drink fermented with multistrain probiotics on antibiotic associated diarrhoea (AAD).
                Double-blind placebo controlled study.
                University Hospital of North Norway.
                Of 853 patients treated with antibiotics, 87 met the inclusion criteria, and were randomized to ingestion of a fermented milk drink containing LGG, La-5 and Bb-12 (n=46) or placebo with heat-killed bacteria (n=41), during a period of 14 days. A diary was recorded, and stool samples were collected for microbiological analyses.
                Sixty-three patients completed the study according to the protocol; two patients (5.9%) in the treatment group and eight (27.6%) in the placebo group developed AAD (P=0.035). The relative risk of developing AAD was 0.21 (95% confidence interval: 0.05-0.93) when given probiotic milk drink.
                A fermented multistrain probiotic milk drink may prevent four of five cases of AAD in adult hospitalized patients.
                TINE BA, Oslo, Norway. Interest to probiotics for the prevention and treatment of antibiotic-associated diarrhea is increasing gradually. The most promising seems to be Saccharomyces boulardii . Using a double-blind controlled study, we investigated the preventive effect of S. boulardii on the development of antibiotic-associated diarrhea in patients under antibiotherapy but not requiring intensive care therapy.
                All the patients were hospitalized at the Gulhane Military Medical Academy, Department of Infectious Diseases and Clinical Microbiology. S. boulardii was given twice daily during the course of antibiotic therapy and application was initiated in all patients as late as after 48 hours of antibiotic therapy. A total of 151 patients completed the study.
                The antibiotic-associated diarrhea development ratio in placebo group was 9% (7/78) and in the study group 1.4% (1/73) (p < 0.05). Stool samples from the patients with antibiotic-associated diarrhea were stored at -70 degrees C and Clostiridium difficile toxin A assay was performed using Enzyme Immune Assay as late as in seven days. C. difficile toxin A assay yielded positive results in two (2/7) stool samples from the patients with antibiotic-associated diarrhea in the placebo group and a negative result in the only patient who developed antibiotic-associated diarrhea in the study group.
                The results implied that prophylactic use of Saccharomyces boulardii resulted in reduced, with no serious side effects, antibiotic-associated diarrhea in hospitalized patients. To examine if intake of Lactobacillus plantarum can prevent gastrointestinal side effects in antibiotic-treated patients.
                Diarrhea is a common side effect of treatment with antibiotics. Some studies indicate that the risk of antibiotic-associated diarrhea can be reduced by administration of certain probiotic microorganisms.
                Patients treated for infections at a university hospital infectious diseases clinic were randomized to daily intake of either a fruit drink with L. plantarum 299v (10(10) colony forming units/d) or a placebo drink, until a week after termination of antibiotic treatment. Subjects recorded the number and consistency of stools as well as gastrointestinal symptoms until up to 3 weeks after last intake of test drink. Fecal samples were collected before the first intake of test drink and after termination of antibiotic therapy and analyzed for Clostridium difficile toxin.
                Clinical characteristics on admission were similar in the 2 groups. The overall risk of developing loose or watery stools was significantly lower among those receiving L. plantarum [odds ratio (OR), 0.69; 95% confidence interval (CI), 0.52-0.92; P=0.012], as was development of nausea (OR, 0.51; 95% CI, 0.30-0.85; P=0.0097). Diarrhea defined as > or =3 loose stools/24 h for > or =2 consecutive days was unaffected by the treatment (OR, 1.4; 95% CI, 0.33-6.0; P=0.86). No significant differences regarding carriage of toxin producing C. difficile were observed between the groups.
                Our results indicate that intake of L. plantarum could have a preventive effect on milder gastrointestinal symptoms during treatment with antibiotics. Antibiotic associated diarrhea (AAD) is a frequently encountered adverse event following antibiotic administration. Evidence suggests that probiotics may be beneficial in preventing and decreasing the severity of AAD.
                Adult patients who were prescribed antibiotics for 3-14 days were enrolled from eight Canadian centers. Study treatment was randomized at a 1 : 1 ratio of BIO-K+CL1285( (®) ) or placebo and was administered within 24 h of initiation to 5 days after termination of antibiotherapy. Patients were followed for 21 days after last dose of study treatment. The primary outcome was severity and incidence of AAD. Severity was measured by the total number of days with diarrhea and incidence was defined as the number of patients with at least one day with diarrhea over the total number of patients enrolled in the study.
                216 patients were randomized to BIO-K+ and 221 to placebo. The mean (SD) number of days with diarrhea was 1.19. (3.20) days for the placebo and 0.67 (2.05) days for BIO-K+CL1285( (®) ) (p = 0.040). Adjusted multivariate linear regression results showed that the duration of diarrhea for BIO-K+CL1285 (®)vs. placebo was reduced by 51.5% (b[SE] = 0.515 [0.256], p = 0.045). The incidence of diarrhea was 21.8% for the BIO-K+ and 29.4% for the placebo group (OR = 0.667, p = 0.067). Multivariate logistic regression, showed that the adjusted odds ratio of AAD in patients receiving BIO-K+ vs. placebo was 0.627 (p = 0.037). Study treatment was well tolerated.
                BIO-K+ is effective for preventing and reducing the severity of AAD in patients receiving antibiotic therapy in a hospital setting. 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. Antibiotic-associated diarrhoea may develop during or following Helicobacter pylori eradication. We aimed to evaluate the efficacy and safety of Saccharomyces boulardii in preventing antibiotic-associated diarrhoea in patients receiving antibiotics for H. pylori eradication.
                In a multicentre prospective clinical trial, patients with peptic ulcer disease or non-ulcer dyspepsia were enrolled to receive clarithromycin, amoxicillin and omeprazole for H. pylori eradication for 14 days. These patients were then randomized to receive either S. boulardii 500 mg twice daily (treatment group) or no treatment (control group). The primary outcome measure was the development of diarrhoea during (treatment period) or within 4 weeks after treatment (follow-up period).
                Of the 389 patients that were enrolled, 376 completed the study. Within the treatment period, diarrhoea developed in 5.9% of patients in the treatment group and in 11.5% of patients in the control group (P = 0.049); and in the follow-up period, diarrhoea developed in 1.0% of patients in the treatment group and in 3.8% of patients in the control group (P = 0.09). Overall diarrhoea rates throughout the whole study period were 6.9% in the treatment group and 15.6% in the control group (P = 0.007). No significant difference was observed between the treatment and control groups in terms of adverse events.
                S. boulardii is an effective and safe treatment for prevention of antibiotic-associated diarrhoea when given concomitantly to patients receiving H. pylori eradication. 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) Saccharomyces boulardii, a nonpathogenic yeast, has been widely used in Europe to prevent antibiotic-associated diarrhea (AAD). We performed a prospective double-blind controlled study to investigate AAD in hospitalized patients and to evaluate the effect of S. boulardii, a living yeast, given in capsule form concurrently with antibiotics. Over 23 mo, 180 patients completed the study. Of the patients receiving placebo, 22% experienced diarrhea compared with 9.5% of patients receiving S. boulardii (p = 0.038). Risk factors found to be associated with AAD were multiple antibiotic combinations (containing clindamycin, cephalosporins, or trimethoprim-sulfamethoxazole) and tube feeding. Clostridium difficile, an anaerobe found in the stools of most patients with pseudomembranous colitis, was variably associated with AAD. We evaluated the role of C. difficile in AAD in the study population and found no significant association between the presence of C. difficile or cytotoxin with AAD. Approximately 33% of the patients without diarrhea harbored at least one C. difficile-positive stool and nearly 50% of these patients had detectable cytotoxin. Similar values were obtained in patients with diarrhea. Of C. difficile-positive patients, 31% (5/16) on placebo developed diarrhea compared with 9.4% (3/32) on S. boulardii; this difference was not statistically significant (p = 0.07). There were no discernable adverse effects of yeast administration. We conclude that S. boulardii reduces the incidence of antibiotic-associated diarrhea in hospitalized patients. Recent studies indicate a potential role of Saccharomyces boulardii in the prevention of Helicobacter pylori treatment-related side-effects and also in improvement of eradication rate. Our aim is to investigate the efficacy and safety of S. boulardii in the prevention of side-effects related to H. pylori eradication. The secondary aim of the study was to define the effect of S. boulardii on the eradication success of anti-H. pylori therapy.
                One hundred and twenty-four patients with H. pylori infection (male/female: 44/80, mean age: 48 +/- 14.25 year) receiving 14 days of triple therapy (clarithromycin 500 mg b.i.d., amoxicillin 1000 mg b.i.d., and lansoprazole 30 mg b.i.d.) were randomly assigned to S. boulardii or placebo. Dyspeptic symptoms were recorded by using modified Glasgow Dyspepsia Questionnaire (GDQ). Side-effect profile and tolerability were assessed using a symptom-based questionnaire. H. pylori status was rechecked after 6 weeks after completion of eradication therapy.
                H. pylori eradication rate, although higher in the treatment group, was statistically similar in treatment and control groups: 71% (44/62) versus 59.7% (37/62), respectively (p > .05). Nine (14.5%) patients in the treatment group and 19 (30.6%) patients in the placebo group experienced diarrhea (p < .05). Epigastric discomfort was more frequent in the control group [9 (14.5%) versus 27 (43.5%), respectively (p < .01)]. Diffuse abdominal pain, abdominal gas, taste disturbance, urticaria, nausea symptoms were similar in both groups. GDQ scores after treatment were significantly better for treatment group (mean +/- SD, range: 1.38 +/- 1.25 (0-5) vs. 2.22 +/- 1.44 (0-6), respectively; p < .01).
                S. boulardii improved anti-H. pylori antibiotherapy-associated diarrhea, epigastric discomfort, and treatment tolerability. In addition, S. boulardii supplement decreased post-treatment dyspepsia symptoms independent of H. pylori status. However, S. boulardii had no significant affect on the rate of H. pylori eradication. To determine the safety and efficacy of a new preventive agent for antibiotic-associated diarrhea (AAD) in patients receiving at least one beta-lactam antibiotic.
                A double-blinded, placebo-controlled, parallel group study was performed in a high-risk group of hospitalized patients receiving a new prescription for a beta-lactam antibiotic and having no acute diarrhea on enrollment. Lyophilized Saccharomyces boulardii or placebo (1 g/day) was given within 72 h of the start of the antibiotic(s) and continued until 3 days after the antibiotic was discontinued, after which the patients were followed for 7 wk.
                Of the 193 eligible patients, significantly fewer, 7/97 (7.2%), patients receiving S. boulardii developed AAD compared with 14/96 (14.6%) on placebo (p = 0.02). The efficacy of S. boulardii for the prevention of AAD was 51%. Using a multivariate model to adjust for two independent risk factors for AAD (age and days of cephalosporin use), the adjusted relative risk was significantly protective for S. boulardii (RR = 0.29, 95% CI = 0.08, 0.98).
                The prophylactic use of S. boulardii given with a beta-lactam antibiotic resulted in a significant reduction of AAD with no serious adverse reactions. Antibiotic-associated diarrhea is an important problem in hospitalized patients. The use of probiotics is gaining interest in the scientific community as a potential measure to prevent this complication. The main objective of the present study was to assess the efficacy and safety of a fermented milk combining Lactobacillus acidophilus and Lactobacillus casei that is widely available in Canada, in the prevention of antibiotic-associated diarrhea.
                In this double-blind, randomized study, hospitalized patients were randomly assigned to receive either a lactobacilli-fermented milk or a placebo on a daily basis.
                Among 89 randomized patients, antibiotic-associated diarrhea occurred in seven of 44 patients (15.9%) in the lactobacilli group and in 16 of 45 patients (35.6%) in the placebo group (OR 0.34, 95% CI 0.125 to 0.944; P=0.05). The median hospitalization duration was eight days in the lactobacilli group, compared with 10 days in the placebo group (P=0.09). Overall, the lactobacilli-fermented milk was well tolerated.
                The daily administration of a lactobacilli-fermented milk was safe and effective in the prevention of antibiotic-associated diarrhea in hospitalized patients. The efficacy of Lactobacillus GG yoghurt in preventing erythromycin associated diarrhoea was studied. Sixteen healthy volunteers were given erythromycin acistrate 400 mg t.i.d for a week. The volunteers were randomly assigned into two groups taking twice daily 125 ml of either Lactobacillus GG fermented yoghurt or pasteurized regular yoghurt as placebo during the drug treatment. Subjects receiving Lactobacillus GG yoghurt with erythromycin had less diarrhoea than those taking pasteurized yoghurt. Other side effects of erythromycin, such as abdominal distress, stomach pain and flatulence, were less common in the GG yoghurt group than in the placebo yoghurt group. The subjects receiving Lactobacillus GG yoghurt were colonized with these bacteria even during erythromycin treatment as measured by faecal counts of total Lactobacillus GG. No Lactobacillus GG was found in the faecal samples of volunteers in the group taking pasteurized yoghurt. Probiotics may be efficacious for the prevention of antibiotic-associated diarrhoea. The tolerability and acceptability of probiotics in an elderly US veteran population has not been assessed.
                To undertake a randomized trial to determine the tolerability and acceptability of a probiotic, Florajen in an elderly population with multiple comorbidities.
                Pilot randomized double-blind trial comparing a probiotic, Florajen to placebo for the prevention of antibiotic-associated diarrhoea in elderly hospitalized patients receiving antibiotics.
                Forty patients were enrolled and randomized. Antibiotic-associated diarrhoea occurred in 6/16 (37%) in the placebo group and 4/23 (17%) patients in the Florajen group, (RR 1.63, 95% CI 0.73-3.65, P = 0.15). Florajen was well tolerated in the study population with no major side effects that necessitated discontinuation.
                In this pilot study, Florajen was well tolerated in an elderly population, all of whom were taking several other medications. A larger study is needed to determine the effect of Florajen on antibiotic-associated diarrhoea and Clostridium difficile infection. Diarrhoea is a common side effect of antibiotic therapy, especially in the elderly. Saccharomyces boulardii is a non-pathogenic yeast which has been demonstrated to reduce the frequency of diarrhoea in patients due to a variety of causes. We set out to assess its role in preventing antibiotic-related diarrhoea. Consecutive patients over the age of 65 admitted to medical wards, and who were being prescribed antibiotics, were randomized to receive either S. boulardii 113 g twice daily or placebo for as long as they received antibiotics. Bowel habit was monitored using a record of interdefaecatory intervals (IDI) and stool form graded 1-4 (hard to liquid). Stool samples were tested every fourth day for Clostridium difficile toxin. Of the 72 patients randomized, 69 completed the study. There was no difference in sex, age, duration of antibiotic use, length of hospital stay, IDI, stool form, the proportion of patients receiving laxatives, the number of patients experiencing watery stools (seven vs. five), or the presence of C. difficile toxin (five vs. three). No side effects were attributable to S. boulardii. There was no evidence that the concomitant use of S. boulardii with antibiotics alters patients' bowel habits or prevents the appearance of C. difficile toxin in the stool. Thus, S. boulardii cannot be recommended as a 'natural' way to prevent antibiotic-related diarrhoea. This highlights the need for proper evaluation of probiotics before their unrestricted use in medical practice. OBJECTIVE: To study the effect of administration of clindamycin with or without supplementation of the intestinal microflora with Bifidobacterium bifidum and Lactobacillus acidophilus. METHODS: Twenty-three healthy subjects received clindamycin by mouth for 7 days. Eleven of the subjects also received capsules containing lyophilized L. acidophilus and B. bifidum for 14 days. The other 12 subjects received placebo. RESULTS: There was a marked decrease in total numbers of anaerobic bacteria during the administration of clindamycin. In the lactic acid bacteria-supplemented group, a tendency towards delayed reduction and earlier increase in bifidobacteria was observed, and two of 11 subjects (18%) were colonized with Clostridium difficile, in comparison with five of 12 (41%) in the placebo group. The total number of microorganisms was significantly higher in the lactic acid bacteria-supplemented group than in the placebo group (p=0.02) 4 days after the end of clindamycin administration. The difference was mainly due to higher counts of Escherichia coli and enterococci. Mean levels of other enterobacteria increased less in the lactic acid bacteria-supplemented group than in the placebo group between days 0 and 14. CONCLUSIONS: The recolonization with aerobic and anaerobic microorganisms was faster in the lactic acid bacteria-supplemented group than in the placebo group. This may be of importance in preventing colonization with C. difficile. Colonic infection with Clostridium difficile, leading to pseudomembranous colitis, is a common complication of antibiotic therapy, especially in elderly patients. It has been suggested that non-pathogenic probiotic bacteria might prevent the development and recurrence of C. difficile infection. This double-blind, placebo-controlled study examines the role of probiotic administration in the prevention of C. difficile-associated diarrhoea (CDAD) in elderly patients receiving antibiotic therapy. Consecutive patients (150) receiving antibiotic therapy were randomised to receive either a probiotic containing both Lactobacillus and Bifidobacterium or placebo for 20 days. Upon admission to hospital, bowel habit was recorded and a faecal sample taken. Trial probiotic or placebo was taken within 72 h of prescription of antibiotics, and a second stool sample was taken in the event of development of diarrhoea during hospitalisation or after discharge. Of the randomised patients, 138 completed the study, 69 with probiotics in conjunction with antibiotics and 69 with antibiotics alone. On the basis of development of diarrhoea, the incidence of samples positive for C. difficile-associated toxins was 2.9% in the probiotic group compared with 7.25% in the placebo-control group. When samples from all patients were tested (rather than just those developing diarrhoea) 46% of probiotic patients were toxin-positive compared with 78% of the placebo group. Standard therapies for antibiotic-associated diarrhea (AAD) and Clostridium difficile-associated diarrhea (CDAD) have limited efficacy. Probiotic prophylaxis is a promising alternative for reduction of AAD and CDAD incidence.
                In this single-center, randomized, double-blind, placebo-controlled dose-ranging study, we randomized 255 adult inpatients to one of three groups: two probiotic capsules per day (Pro-2, n=86), one probiotic capsule and one placebo capsule per day (Pro-1, n=85), or two placebo capsules per day (n=84). Each probiotic capsule contained 50 billion c.f.u. of live organisms (Lactobacillus acidophilus CL1285 +Lactobacillus casei LBC80R Bio-K+ CL1285). Probiotic prophylaxis began within 36 h of initial antibiotic administration, continued for 5 days after the last antibiotic dose, and patients were followed for an additional 21 days.
                Pro-2 (15.5%) had a lower AAD incidence vs. Pro-1 (28.2%). Each probiotic group had a lower AAD incidence vs. placebo (44.1%). In patients who acquired AAD, Pro-2 (2.8 days) and Pro-1 (4.1 days) had shorter symptom duration vs. placebo (6.4 days). Similarly, Pro-2 (1.2%) had a lower CDAD incidence vs. Pro-1 (9.4%). Each treatment group had a lower CDAD incidence vs. placebo (23.8%). Gastrointestinal symptoms were less common in the treatment groups vs. placebo and in Pro-2 vs. Pro-1.
                The proprietary probiotic blend used in this study was well tolerated and effective for reducing risk of AAD and, in particular, CDAD in hospitalized patients on antibiotics. A dose-ranging effect was shown with 100 billion c.f.u., yielding superior outcomes and fewer gastrointestinal events compared to 50 billion c.f.u. (ClinicalTrials.gov number NCT00958308). Antibiotic associated diarrhea due to human intestinal microbiota abnormalities is a side effect of H. pylori eradication therapy. We examined intestinal microbiota changes during H. pylori eradication therapy and the preventive effect of CBM588 as a probiotic agent. Nineteen patients with gastro-duodenal ulcer were randomly divided into three groups: group A (without probiotics), group B (with regular doses of CBM588) and group C (with double doses of CBM588). The incidence of diarrhea and soft stools during H. pylori eradication therapy was 43% in group A and 14% in group B, while none of the patients in group C reported diarrhea or soft stools. Both bacterial counts and detection rates of bifidobacteria and/or obligate anaerobe were decreased by eradication therapy. However, bacterial counts of obligate anaerobes in group C were significantly higher than in group A (P < 0.05). Additionally, during eradication therapy C. difficile toxin A was detected in both group A and group B but not in group C. In conclusion, these results indicate that H. pylori eradication therapy induces antibiotic associated diarrhea due to abnormalities in intestinal microbiota and/or C. difficile. However, these side effects might be prevented by probiotics. To investigate the effect of probiotic bacterium, Clostridium butyricum MIYAIRI 588 strain (CBM) on the changes of the fecal flora in Helicobacter pylori (H. pylori) treatment.
                Thirty-five patients with gastric or duodenal ulcers positive for H. pylori were randomized either to 1 wk amoxicillin, clarithromycin, lansoprazole (Group 1) or to the same regimen supplemented with CBM 7 d ahead of the triple therapy (Group 2). Stool samples were collected before and 2, 4, 7, 15, and 22 d after the starting eradication therapy, and were examined intestinal flora. Patients were required to keep a diary record of their condition.
                Obligate anaerobes decreased significantly on d 2, 4, 8 and 15 in Group 1. On the other hand, they did not decrease significantly in Group 2. The Escherichia coli was dominant bacterium in Enterobacteriaceae, but that was replaced by other species such as Klebsiella and Enterobacter after eradication in Group 1. The change was suppressed in Group 2. Abdominal symptoms were less frequent in Group 2 than in Group 1.
                The combined use of CBM reduced the changes in the intestinal flora and decreased the incidence of gastrointestinal side effects. 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.
Based on this systematic review and meta-analysis of 23 randomized controlled trials including 4213 patients, moderate quality evidence suggests that probiotics are both safe and effective for preventing Clostridium difficile-associated diarrhea.