Prevention Of Antibiotic-associated Diarrhea Research Articles

Effect of ProbioticLactobacillus(Lacidofil® Cap) for the Prevention of Antibiotic-associated Diarrhea: A Prospective, Randomized, Double-blind, Multicenter Study

Antibiotic-associated diarrhea (AAD) is a common complication of antibiotic use. There is growing interest in probiotics for the treatment of AAD and Clostridium difficile infection because of the wide availability of probiotics. The aim of this multicenter, randomized, placebo-controlled, double-blind trial was to assess the efficacy of probiotic Lactobacillus (Lacidofil® cap) for the prevention of AAD in adults. From September 2008 to November 2009, a total of 214 patients with respiratory tract infection who had begun receiving antibiotics were randomized to receive Lactobacillus (Lacidofil® cap) or placebo for 14 days. Patients recorded bowel frequency and stool consistency daily for 14 days. The primary outcome was the proportion of patients who developed AAD within 14 days of enrollment. AAD developed in 4 (3.9%) of 103 patients in the Lactobacillus group and in 8 (7.2%) of 111 patients in the placebo group (P=0.44). However, the Lactobacillus group showed lower change in bowel frequency and consistency (50/103, 48.5%) than the placebo group (35/111, 31.5%) (P=0.01). Although the Lacidofil® cap does not reduce the rate of occurrence of AAD in adult patients with respiratory tract infection who have taken antibiotics, the Lactobacillus group maintains their bowel habits to a greater extent than the placebo group.

Saccharomyces boulardii in childhood

Probiotics are live microorganisms which confer a health benefit on the host. Saccharomyces boulardii, a yeast, has been found to be an effective probiotic in double-blind placebo-controlled randomized clinical studies. We reviewed the established mechanisms of actions and clinical efficacy in children of S. boulardii. The mechanisms of action of S. boulardii depend mainly on the inhibition of some bacterial toxins, anti-inflammatory effects, and on stimulating effects on the intestinal mucosa such as trophic effects on the brush border enzymes and immunostimulatory effects. At present, in pediatric populations, there is evidence that S. boulardii is beneficial for the treatment of acute gastroenteritis and the prevention of antibiotic-associated diarrhea. More data are needed in other indications such as traveller's diarrhea, Helicobacter pylori eradication, and inflammatory bowel disease. S. boulardii is a yeast strain that has been extensively studied in vitro and in vivo. Recent data have opened the door for new therapeutic indications.

Probiotics in Allergy Management

The gut contains a diverse bacterial flora that is acquired at birth and has a number of physiological functions. Administration of prebiotics or probiotics may favourably alter this gut microflora. Prebiotics are poorly digested oligosaccharides that promote the growth of desirable bacteria and may have other beneficial gastrointestinal and systemic effects. Probiotics are "helpful" human bacteria that provide a variety of health benefits when administered exogenously. Probiotics produce beneficial effects in the prevention and treatment of traveller's diarrhoea, viral diarrhoea, and diarrhoea in day care centres. Moreover, probiotics have been shown to reduce relapses associated with Clostridium difficile, and Lactobacilli are effective in the prevention of antibiotic-associated diarrhoea. Probiotics may also be efficacious in the treatment of gastroenteritis. Clinical studies of probiotics in inflammatory bowel disease have proved disappointing, but beneficial effects in adults with irritable bowel syndrome have been reported with Bifidobacterium infantis 35624. Lactobacilli GG reduces the incidence of gastrointestinal symptoms and gut permeability in patients with atopic dermatitis, and administration of probiotics reduces the frequency and severity of atopic eczema when administered to pregnant women and then to newborn infants. In conclusion, probiotics are effective in the treatment and/or prevention of a number of conditions, including diarrhoea, irritable bowel syndrome and atopic dermatitis, and the product used should be selected based on the particular indication.

Effect of probiotic Saccharomyces boulardii on prevention of antibiotic-associated diarrhea in adult outpatients with amoxicillin treatment

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.

Probiotics for Prevention of Antibiotic-associated Diarrhea

Antibiotic-associated diarrhea (AAD) occurs in approximately 25% of patients receiving antibiotics. Hospitalized patients with AAD are at increased risk for nosocomial infections and have a higher mortality. Probiotics are living microorganisms used to restore gut health by changing the intestinal microbiota. Several have been studied for the prevention of AAD. Five meta-analyses of trials of probiotics for the prevention of AAD have been performed. The results showed an overall reduction in the risk of AAD when probiotics were coadministered with antibiotics. McFarland conducted the largest meta-analysis to date analyzing 25 randomized controlled trials of probiotics for the prevention of AAD including 2810 subjects. More than half of the trials demonstrated efficacy of the probiotic. In particular, Lactobacillus GG, Saccharomyces boulardii, and the probiotic mixtures were effective. The Cochrane Database of Systematic Reviews published a review of the literature on the use of probiotics for the prevention of pediatric AAD, including 10 randomized trials testing 1986 children. The per protocol pooled analysis, but not the intent-to-treat analysis, showed that probiotics are effective for preventing AAD with the number needed to treat to prevent 1 case of diarrhea being 10. Lactobacillus GG, Bacillus coagulans, and S. boulardii appeared to be most effective. Probiotics are generally safe, however, they should be used with caution in patients who have compromise of either the immune system or the integrity of the intestinal mucosa, and in the presence of a central venous catheter.

Recommendations for Probiotic Use—2008

Recommendations for the clinical use of probiotics were published after a Yale University Workshop in 2005. A similar workshop was held in 2007, and the recommendations were updated and extended into other areas. The recommendations are graded into an "A," "B," "C" or no category based on the expert's opinion and review by the workshop participants. An "A" recommendation is made for acute childhood diarrhea, prevention of antibiotic-associated diarrhea, preventing and maintaining remission in pouchitis, and in an immune response for the treatment and prevention of atopic eczema associated with cow's milk allergy. The group maintained several "B" recommendations in other areas of treating inflammatory bowel disease and irritable bowel syndrome. Although there are significant studies in the "B" group, most "B" recommendations did not reach an "A" level because of some negative studies or a limited number of studies. Many reports in the "C" recommendations were significant but fell short of receiving stronger ratings because of the size of reported patient studies, and also the factors that limited categories to the "B" rating.

Prevention of antibiotic-associated diarrhoea by a fermented probiotic milk drink

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.

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.

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 clinical utility of probiotics for the prevention of antibiotic-associated diarrhea remains to be established conclusively

The clinical utility of probiotics for the prevention of antibiotic-associated diarrhea remains to be established conclusively

Probiotics in the prevention of antibiotic-associated diarrhea in children: A meta-analysis of randomized controlled trials

To systematically evaluate the effectiveness of probiotics in preventing antibiotic-associated diarrhea (AAD) in children. The following electronic databases up to December 2005, in any language, were searched for studies relevant to AAD and probiotics: MEDLINE, EMBASE, and The Cochrane Library. Only randomized controlled trials (RCT) were considered for study inclusion. Six placebo-controlled, RCTs (766 children) were included. Treatment with probiotics compared with placebo reduced the risk of AAD from 28.5% to 11.9% (relative risk, RR, 0.44, 95% CI 0.25 to 0.77, random effect model). Preplanned subgroup analysis showed that reduction of the risk of AAD was associated with the use of Lactobacillus GG (2 RCTs, 307 participants, RR 0.3, 95% CI 0.15 to 0.6), S. boulardii (1 RCT, 246 participants, RR 0.2, 95% CI 0.07-0.6), or B. lactis & Str. thermophilus (1 RCT, 157 participants, RR 0.5, 95% CI 0.3 to 0.95). Probiotics reduce the risk of AAD in children. For every 7 patients that would develop diarrhea while being treated with antibiotics, one fewer will develop AAD if also receiving probiotics.

Meta–but not the final–analysis of efficacy of probiotics in prevention of antibiotic-associated diarrhea

The meta-analysis performed by Szajewska et al included only placebo-controlled, randomized clinical trials of efficacy of probiotics in preventing antibiotic-associated diarrhea in children. The expected quality of the studies and findings, therefore, would be high. The authors point out that unfortunately, precision of definition of diarrhea, the classes of antibiotics used, the species of probiotic microorganism used were heterogeneous across studies. Although the use of probiotics was associated with relative risk of 0.44 (95% confidence interval 0.25 to 0.77) for antibiotic associated diarrhea, there are several caveats of study design that preclude their definitive recommendation. Larger, better studies are necessary to form the evidence before the next metaanalysis can be performed, which conclusion could guide optimal clinical care.

Meta-Analysis of Probiotics for the Prevention of Antibiotic Associated Diarrhea and the Treatment of Clostridium difficile Disease

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.

Recommendations for Probiotic Use

Probiotics are live microbial organisms that are administrated as supplements or in foods to benefit the host. It is the recommendation that they may be helpful in the prevention and treatment of acute diarrhea in adults and children, the prevention of antibiotic-associated diarrhea in adults and children, and the maintenance of remission and prevention of pouchitis. Although early results indicate that probiotics may also be useful in immunologic modulation to prevent atopy, treatment of radiation intestinal disease, vaginosis, ulcerative colitis, and the irritable bowel syndrome, the studies available are not sufficient to say they are definitely helpful. Even fewer data are available to recommend probiotics for the treatment of H pylori and Crohn disease and for the prevention of cardiovascular risk factors or other degenerative diseases. Clearly, larger and better-designed studies of probiotics are necessary, including comparative and dose-ranging trials.

Probiotic therapy for the prevention and treatment of Clostridium difficile-associated diarrhea: a systematic review

The recent increase in the number and severity of cases of nosocomial Clostridium difficile-associated diarrhea (CDAD) has prompted interest in the use of probiotics for the prevention and treatment of this disease. We performed a systematic review of randomized controlled trials to assess the effectiveness of probiotic therapy. We searched the PubMed, EMBASE, INAHTA, HEN and Cochrane Collaboration databases to identify trials in which the prevention or treatment of CDAD with probiotic therapy was the primary or secondary outcome. We extracted data on the number of patients randomly assigned to receive probiotic or placebo, the number of patients with CDAD, the type of probiotic, criteria for diagnosing CDAD, persistence of infection after treatment, compliance and adverse effects. We identified 4 eligible studies in which prevention (n = 1) or treatment (n = 3) of CDAD was the primary outcome. The benefit of probiotic therapy seen in 2 of the studies was restricted to subgroups characterized by severe CDAD and increased use of vancomycin. The remaining 2 studies were too methodologically flawed for us to draw meaningful conclusions. We also identified 4 trials in which prevention of antibiotic-associated diarrhea with probiotics was the primary outcome and prevention of CDAD a secondary outcome. These studies were limited primarily by too few CDAD cases and provided no evidence of effective prophylaxis. Overall, heterogeneity in choice and dose of probiotic and in criteria for diagnosing CDAD makes it difficult to synthesize information from the 8 studies. Studies conducted to date provide insufficient evidence for the routine clinical use of probiotics to prevent or treat CDAD. Better designed and larger studies are needed.

Saccharomyces boulardii and antibiotic‐associated diarrhoea in children

Sirs, We read with great interest the recent paper by Kotowska et al.1 about Saccharomyces boulardii (S. boulardii) in the prevention of antibiotic-associated diarrhoea (AAD) in children. The study adds important information about probiotic prophylaxis for AAD in children. Authors reported that treatment with S. boulardii had been given twice daily (500 mg/day) for the duration of the antibiotic treatment in 269 children, and it was concluded that S. boulardii had reduced the overall risk of AAD from 17.3% to 3.4% when compared with the control group.1 A randomized, controlled study concerning the efficacy of S. boulardii as an adjunct to sulbactam-ampicillin (SAM) or azithromycin for prophylaxis of AAD in 466 children, was conducted by our clinic2 but not discussed by Kotowska et al. We showed that S. boulardii taken once daily (250 mg/day) significantly decreased the AAD rate from 25.6% to 5.7% in children receiving SAM. The highest rate of AAD was in children treated with SAM and who were below six years of age, so we suggested the use of S. boulardii at the dose of 250 mg/day as an adjunct to SAM – especially at this age group for prevention of AAD.

Does Lactobacillus GG prevent antibiotic-associated diarrhea in children?

Does Lactobacillus GG prevent antibiotic-associated diarrhea in children?

Probiotics: Not Just for Treatment Anymore

Probiotics, microorganisms that can have positive health effects when ingested, are increasingly studied and used in humans. Thus far, they have shown particular promise in the treatment of acute infectious diarrhea and the prevention of antibiotic-associated diarrhea, associations that have been investigated widely and have been subject to systematic review.1–4 Other conditions potentially treatable by probiotics include chronic diarrhea,5 inflammatory bowel disease,6 irritable bowel syndrome,7 and food allergy8; potentially preventable conditions range from travelers’ diarrhea9 and necrotizing enterocolitis10 to urogenital infections,11 atopic diseases,12 and dental caries.13 Vanderhoof14 and other leaders in the field propose future applications in cystic fibrosis, rheumatoid arthritis, and cancers. The study reported by Weizman et al15 in this issue of Pediatrics is one of a handful of randomized, controlled trials that have examined probiotics as a prevention for acute infectious illnesses in otherwise healthy infants and children.16–20 This study aims to investigate whether a so-called functional food, infant formula containing either Bifidobacterium lactis or Lactobacillus reuteri , can decrease the risk of diarrhea, respiratory symptoms, fever, and other “morbidity parameters” when compared with a placebo formula. This represents a plausible future real-world scenario: infants attending child care centers, who may be at increased risk of these illnesses, could receive regular prophylaxis in the form of probiotic formula. The authors report a decrease in the numbers of episodes and numbers of days of both diarrhea and fever in the probiotic groups when compared with the placebo group. For example, the subjects in the placebo, B lactis , and L reuteri groups averaged 0.59, 0.37, and 0.15 days with diarrhea (presumably per child during the 12-week study period), respectively. This finding is interesting, although … Address correspondence to Cornelius W. Van Niel, MD, Sea Mar Community Health Centers, 8720 14th Ave S, Seattle, WA 98108. E-mail: cvanniel{at}u.washington.edu

Probiotics and gastrointestinal diseases

There is increasing evidence indicating health benefits by consumption of foods containing microorganisms, i.e. probiotics. A number of clinical trials have been performed to evaluate the effects in the prevention and treatment of gastrointestinal diseases caused by pathogenic microorganisms or by disturbances in the normal microflora. Gastrointestinal infections caused by Helicobacter pylori, traveller's diarrhoea, rotavirus diarrhoea, antibiotic-associated diarrhoea (AAD) and Clostridium difficile-induced diarrhoea are conditions that have been studied. There are also studies performed on the preventive effect of probiotics on radiation-induced diarrhoea and diarrhoea in tube-fed patients. Inflammatory bowel disease and irritable bowel syndrome, two idiopathic conditions where alterations in the normal microflora have been implicated as responsible for initiation, are two further areas where the use of probiotics has been regarded as promising. The results from clinical studies have not been conclusive in that the effects of probiotics have been strain-dependent and different study designs have been used. Treatment of acute diarrhoea in children and prevention of AAD are the two most justified areas for the application of probiotics.

Diarrhées associées aux antibiotiques chez le sujet âgé

Purpose. – Most of the antibiotic-associated diarrhea (AAD) cases result from a transient disturbance in the function of the normal intestinal flora and are spontaneously solved when discontinuing the antibacterial therapy. However, a mild diarrhea lasting several days may induce a dehydration or worsen a denutrition in frail elderly people. Current knowledge and key points. – The incidence of AAD varies between 5 and 25% depending on the concerned antibiotic. Only 10–20% of all AAD cases are caused by infection, especially with Clostridium difficile, for which advanced age is a major risk factor. The first biological exam to perform when severe AAD or in frail people is the detection of C. difficile toxins, especially in elderly patient treated with beta-lactam antibiotics. Nevertheless, other infectious organisms causing AAD may be considered, as Staphylococcus aureus when predominant in stool cultures from patients treated with fluoroquinolones or as Klebsiella oxytoca when isolated in bloody diarrhea from patients treated with ampicillin. Elevated fecal counts of Candida spp. found in patients treated with antibiotics is rather the consequence of therapy than the cause of AAD. The prevention of AAD is based on a rational antibiotic use to avoid endogenous selection of C. difficile and on the improvement of the hygiene measures to limit the exogenous transmission of the bacteria or related spores by spoiled hands. Future prospects. – Simultaneous prescription of non-pathogenic living organisms, capable of re-establishing the equilibrium of the intestinal flora, should be better described, especially in elderly people, because of its important economic impact.

Probiotics, antibiotic-associated diarrhoea and Clostridium difficile diarrhoea in humans

Probiotics are living organisms which, when ingested, have a beneficial therapeutic effect. Examples are bacteria, especially Lactobacillus rhamnosus GG, and the yeast Saccharomyces boulardii. Controlled trials indicate a benefit of both of these in the prevention of antibiotic-associated diarrhoea. Other less effective probiotics are Lactinex, Enterococcus faecium and bifidobacteria. In the difficult clinical problem of recurrent Clostridium difficile disease, S. boulardii as an adjunct to antibiotics has shown benefit in controlled trials. There is, however, less convincing evidence for the efficacy of Lactobacillus GG in this disease. Additional controlled trials and safety studies are needed before there can be a widespread endorsement of probiotics for these two conditions.