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      Meta-analysis of probiotics for the prevention of antibiotic associated diarrhea and the treatment of Clostridium difficile disease.

      The American Journal of Gastroenterology

      Anti-Bacterial Agents, adverse effects, Clostridium difficile, Diarrhea, etiology, microbiology, prevention & control, Enterocolitis, Pseudomembranous, therapy, Humans, Probiotics, therapeutic use

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          Abstract

          Antibiotic-associated diarrhea (AAD) is a common complication of most antibiotics and Clostridium difficile disease (CDD), which also is incited by antibiotics, is a leading cause of nosocomial outbreaks of diarrhea and colitis. The use of probiotics for these two related diseases remains controversial. To compare the efficacy of probiotics for the prevention of AAD and the treatment of CDD based on the published randomized, controlled clinical trials. PubMed, Medline, Google Scholar, NIH registry of clinical trials, metaRegister, and Cochrane Central Register of Controlled Trials were searched from 1977 to 2005, unrestricted by language. Secondary searches of reference lists, authors, reviews, commentaries, associated diseases, books, and meeting abstracts. Trials were included in which specific probiotics given to either prevent or treat the diseases of interest. Trials were required to be randomized, controlled, blinded efficacy trials in humans published in peer-reviewed journals. Trials that were excluded were pre-clinical, safety, Phase 1 studies in volunteers, reviews, duplicate reports, trials of unspecified probiotics, trials of prebiotics, not the disease being studied, or inconsistent outcome measures. Thirty-one of 180 screened studies (totally 3,164 subjects) met the inclusion and exclusion criteria. One reviewer identified studies and abstracted data on sample size, population characteristics, treatments, and outcomes. From 25 randomized controlled trials (RCTs), probiotics significantly reduced the relative risk of AAD (RR = 0.43, 95% CI 0.31, 0.58, p < 0.001). From six randomized trials, probiotics had significant efficacy for CDD (RR = 0.59, 95% CI 0.41, 0.85, p = 0.005). A variety of different types of probiotics show promise as effective therapies for these two diseases. Using meta-analyses, three types of probiotics (Saccharomyces boulardii, Lactobacillus rhamnosus GG, and probiotic mixtures) significantly reduced the development of antibiotic-associated diarrhea. Only S. boulardii was effective for CDD.

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          Most cited references 40

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          Systematic reviews in health care: Assessing the quality of controlled clinical trials.

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            Health care costs and mortality associated with nosocomial diarrhea due to Clostridium difficile.

            A total of 271 patients were prospectively followed up to determine whether patients whose hospital stay is complicated by diarrhea due to Clostridium difficile experience differences in cost and length of stay and survival rates when compared with patients whose stay is not complicated by C. difficile-associated diarrhea. Forty patients (15%) developed nosocomial C. difficile-associated diarrhea. These patients incurred adjusted hospital costs of $3669--that is, 54% (95% confidence interval [CI], 17%-103%)--higher than patients whose course was not complicated by C. difficile-associated diarrhea. The extra length of stay attributable to C. difficile-associated diarrhea was 3.6 days (95% CI, 1.5-6.2). C. difficile-associated diarrhea was not associated with excess 3-month or 1-year mortality after adjustment for age, comorbidity, and disease severity. On the basis of the findings of this study, a conservative estimate of the cost of this disease in the United States exceeds $1.1 billion per year.
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              Lactobacillus GG in the prevention of antibiotic-associated diarrhea in children.

              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.
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                Author and article information

                Journal
                16635227
                10.1111/j.1572-0241.2006.00465.x

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