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. Saccharomyces boulardii for the prevention of antibiotic-associated diarrhea in adult hospitalized patients: a single-center, randomized, double-blind, placebo-controlled trial. Prevention of antibiotic-associated diarrhea by Saccharomyces boulardii: a prospective study. Use of probiotic Lactobacillus preparation to prevent diarrhoea associated with antibiotics: randomised double blind placebo controlled trial. Prophylactic Saccharomyces boulardii in the prevention of antibiotic-associated diarrhea: a prospective study. Treatment of Clostridium difficile associated diarrhea and colitis with an oral preparation of teicoplanin; a dose finding study. The Swedish CDAD Study Group. Saccharomyces boulardii in the prevention of antibiotic-associated diarrhoea in children: a randomized double-blind placebo-controlled trial. Probiotic Escherichia coli Nissle 1917 versus placebo for treating diarrhea of greater than 4 days duration in infants and toddlers.
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 (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. 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. 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. 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. 92 patients with antibiotic-associated diarrhea were randomized to receive oral teicoplanin 100 mg twice daily for 7 days (BID group); or 50 mg 4 times daily for 3 days, followed by 100 mg twice daily for 4 days (QID group) in a randomized, double-blind, multicentre study. Clostridium difficile was demonstrated by culture and/or cytotoxin test in 49 (53%) patients, of whom 47 (23 male, 24 females, mean age 65 years; 23 in the BID group, 24 in the QID group) were evaluable for clinical efficacy. Prior treatment with cephalosporins was registered in 49%, isoxazolyl-penicillins in 33% and clindamycin in 20% of the C. difficile positive patients. On the last day of treatment, 96% (23 of 24 patients) in the QID group were found cured, compared with 70% (16 of 23 patients) in the BID group (p = 0.02). On days 2 and 3 of treatment, QID group patients had significantly fewer loose stools per day (p < 0.05) than those of the BID group. Clinical recurrence, within 4 weeks post-treatment, occurred in 35% and 33% of the patients in the BID and QID groups, respectively. The bacteriological elimination rate 4 weeks post-treatment was 55% in the BID group and 59% in the QID group. The study was terminated prematurely due to the unexpectedly high clinical failure and recurrence rate in C. difficile positive patients treated with the BID dosage regimen. 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. Administering probiotics can prevent or cure some forms of diarrhea. The efficacy of probiotic Escherichia coli Nissle 1917 (EcN) in infants and toddlers with diarrhea >4 days was tested by a double-blind trial.
                One hundred fifty-one children aged 1-47 months with nonspecific diarrhea were randomized to receive either EcN suspension (N = 75) or placebo (N = 76). Diarrhea had to meet the following definition: >3 watery or loose nonbloody stools in 24 hours of a diarrheal episode persisting for >4 consecutive days but < or =14 days. All children were well nourished or only moderately malnourished, mildly dehydrated, and received oral rehydration at study commencement. They were treated orally with 1-3 mL EcN suspension (1 mL contains 10 viable cells) or placebo daily for 21 days. Primary objective was to confirm a better response rate (reduction of daily stool frequency to < or =3 watery or loose stools over > or =4 days) with EcN.
                The 7-day response was higher for the EcN group than placebo (EcN 78.7%, placebo 59.2%). Significant differences were observed on days 14 (EcN 93.3%, placebo 65.8%, P = 0.0017) and 21 (EcN 98.7%, placebo 71.1%, P < 0.001). Kaplan-Meier survival analysis resulted in a significant difference of 3.3 days between the groups (P < 0.0001); median time to response for EcN was 2.4 and 5.7 for placebo. EcN was safe and well tolerated.
                In the conditions of this trial EcN was a suitable remedy for diarrhea >4 days in young 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.