Effect of Lactobacillus Reuteri DSM 17938 to Prevent Antibiotic-associated Diarrhea in Children
Condition: Antibiotic Associated Diarrhea
MeSH terms: Diarrhea
Study type: Interventional
Phase: Phase 4

Summary: 
      Recent studies showed that intestinal microbiota consist more than thousand bacteria, and
      these microorganisms play the role as balance and continuity of the anatomical and functional
      integrity gastrointestinal tract. Chronic diseases, nutritional factors, lifestyle factors
      and medications including antibiotics changes the host microbiota in short or long-term
      period. Antibiotics are the most commonly used drugs in pediatrics routine practice. Although
      frequency and severity of side effects alter the choice of drug, mild complications may be
      taken into consideration for treatment by a physician in the profit and loss balance. Our
      study group (PROBAGE Working Group) have been recently showed that Lactobacillus reuteri DSM
      17938 reduced the duration of diarrhea in children with acute infectious diarrhea, and are
      safe and well-tolerated. In this study the investigators aim to evaluate the potential effect
      of Lactobacillus reuteri DSM 17938 on the prevention of antibiotic associated diarrhea in
      children.
    

Detailed description: 
      Recent studies showed that intestinal microbiota consist more than thousand bacteria, and
      these microorganisms play the role as balance and continuity of the anatomical and functional
      integrity gastrointestinal tract. Chronic diseases, nutritional factors, lifestyle factors
      and medications including antibiotics changes the host microbiota in short or long-term
      period. Antibiotics are the most commonly used drugs in pediatrics routine practice. Although
      frequency and severity of side effects alter the choice of drug, mild complications may be
      taken into consideration for treatment by a physician in the profit and loss balance.

      Antibiotic-associated diarrhea is one of the side effects that occur during antibiotic use,
      the frequency varies according to region and antibiotic type. Aminopenicillins,
      cephalosporins and clindamycin antibiotics has been identified as the most affected group of
      antibiotic-associated diarrhea. Development of antibiotic associated diarrhea are associated
      with the intestinal microbiota balance , the mucosal integrity and changes of vitamin /
      mineral metabolism 3. Majority cases with antibiotic associated diarrhea admit with the
      complaints of abdominal crampy pain and diarrhea while pseudomembranous enterocolitis, in
      severe cases, even death have been reported. Antibiotic-associated diarrhea can be occur
      during antibiotic treatment but may seen at 2-3 weeks later after termination of treatment.
      Broad-spectrum antimicrobial agents have been related 11-40% of antibiotic associated
      diarrhea cases in children.

      In Turkey there are no large studies on the frequency of antibiotic associated diarrhea in
      children, but antibiotics are the most commonly used drug classes in childhood. The use of
      broad-spectrum antibiotics, which creates more risk than narrow-spectrum antibiotics, and the
      highest risk have been observed during use of clindamycin, cephalosporins and
      fluoroquinolones. However, there is no consensus about which antibiotics which are high risk
      or which have significant negative impact on the microbiota. Antibiotic-associated diarrhea,
      has been shown to increase the growth of enteropathogens after antibiotic use.

      In particular, Clostridium difficile (C. difficile) infections are the most common infections
      which related with antibiotic associated diarrhea 2. Although C. difficile diarrhea mostly
      occurs in adults and hospitalized immunocompromised patients, it can be seen in children.

      C. difficile leads to mild diarrhea to pseudomembranous colitis according to toxins. C.
      difficile associated 10-20% of all antibiotic-associated diarrhea forms and can be seen until
      after eight weeks of treatment with antibiotics. Antibiotics disrupt the integrity of the
      normal colonic mucosa, affect carbohydrate metabolism as a result of antimicrobial activity
      in the colon leads to the development of osmotic diarrhea and pathogenic bacteria associated
      diarrhea. The slowing of the metabolism of carbohydrates results in the reduction of
      short-chain fatty acids in the intestinal lumen and cause accumulation of carbohydrates which
      can not be absorbed. Besides the harm normal microbiota have provided the protective barrier
      and intestinal system becomes sensitive to resistant microorganisms. Reduction of intestinal
      lumen and in the number of Bacteroides and Bifidobacteria strains of facultative anaerobes
      (Fusobacterium the Clostridia, Eubacteria) results in the increase. Antibiotic-associated
      diarrhea, alongside a negative effect on the quality of life of the host, the cost of
      treatment in patients hospitalized in the hospital and also negatively affects the length of
      stay.

      In case of outpatient treatment, or in hospitalized patients, antibiotic treatment usually is
      terminated or is changed, it affects the success of the treatment in this case and leads to a
      longer stay in hospital. Especially the long-term hospitalization in the intensive care unit
      at the hospital caused by an increase in the risk of nosocomial infections and has been shown
      to cause mortality 14.

      In case of diarrhea in patients treated ambulatory during treatment if the patient's symptoms
      also declined, antibiotic treatment is interrupted by family. If cases can result in use
      therefore again brought to the physician if the physician broader spectrum antibiotics or
      parenteral drugs.

      In studies with probiotics, some of the probiotic strains of antibiotic-associated diarrhea
      development when used in combination with antibiotics it has been shown to be significantly
      reduced. Harvard / Yale probiotic Workshop Group, World Gastroenterology Organization in the
      prevention of antibiotic associated diarrhea probiotic strains showed that the level of
      evidence A1. However, probiotics effects are strain specific. Although Saccharomyces
      boulardii and Lactobacillus GG are well known strains for prevention of antibiotic associated
      diarrhea, knowledge about the Lactobacillus reuteri DSM 17938 is limited.

      Our study group (PROBAGE Working Group) have been recently showed that Lactobacillus reuteri
      DSM 17938 reduced the duration of diarrhea in children with acute infectious diarrhea, and
      are safe and well-tolerated. In this study the investigators aim to evaluate the potential
      effect of Lactobacillus reuteri DSM 17938 on the prevention of antibiotic associated diarrhea
      in children.
    

Intervention name(s): Lactobacillus reuteri DSM 17938; Placebo; Amoxicillin-Clavulanic Acid
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Comparison the effects of Lactobacillus reuteri DSM 17938 and placebo for prevention of antibiotic associated diarrhea and also plan to compare the duration of treatment for on efficacy.; Comparison the effects of Lactobacillus reuteri DSM 17938 and placebo for prevention of antibiotic associated diarrhea and also plan to compare the duration of treatment for on; All study patients will received amoxicillin-clavulanic acid at the dose of 50-90 mg/kg/day.
Other intervention name(s): BioGaia; Co-amoxilav
Intervention MeSH terms: Amoxicillin; Clavulanic Acids; Clavulanic Acid; Amoxicillin-Potassium Clavulanate Combination
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: Antibiotic associated diarrhea; Children; Prevention; Lactobacillus reuteri DSM 17938; Probiotic