1. The use of Probiotics in the prevention of Antibiotic-Associated Diarrhea Evidence Based Medicine Lindsey Bowman

2. QUESTION - Children or adults receiving antibiotic treatment for any reason. P - Children or adults receiving antibiotic treatment for any reason. I - Co-treating with a probiotic C - Solely treating with antibiotic therapy O - Prevention of antibiotic associated diarrhea, three or more loose stools per day for at least two consecutive days within 12 days of starting the antibiotics.

3. Purpose To determine if co-treating a patient with probiotics while on antibiotic therapy decreases the incidence of antibiotic- associated diarrhea. To determine if co-treating a patient with probiotics while on antibiotic therapy decreases the incidence of antibiotic- associated diarrhea.

4. Why? #1 It’s a commonly asked question in the office. #2 If the solution to preventing antibiotic- associated diarrhea is as simple as co- treating with a probiotic, then why isn’t it required when prescribing antibiotics? #3 AAD occurs in up to 30% of the population treated with antibiotics (Szajewska, 2005).

5. Background - There are no current guidelines delineating a specific protocol for the prevention of AAD. - There are no current guidelines delineating a specific protocol for the prevention of AAD. - Preventive measures include prescribing antibiotics only when necessary, therefore preventing the number of possible cases. - Preventive measures include prescribing antibiotics only when necessary, therefore preventing the number of possible cases.

6. What is AAD? Antibiotic-Associated Diarrhea is three or more loose stools per day for at least two consecutive days within 12 days of starting the antibiotics. Antibiotic-Associated Diarrhea is three or more loose stools per day for at least two consecutive days within 12 days of starting the antibiotics.

7. Why does AAD occur? ~ 25% of cases are attributed to bacterial overgrowth ~ 25% of cases are attributed to bacterial overgrowth ~ 80% of cases are due to a “non-specific cause” ~ 80% of cases are due to a “non-specific cause” (Hawrelak, 2005)

8. Bacterial Overgrowth Destruction of specific types of bacteria in the colon due to the original antibiotic treatment. Destruction of specific types of bacteria in the colon due to the original antibiotic treatment. This allows for other naturally occurring bacteria, most commonly Clostridium difficile to grow unchecked. This allows for other naturally occurring bacteria, most commonly Clostridium difficile to grow unchecked. Causing a bacterial infection causing diarrhea. Causing a bacterial infection causing diarrhea.

9. “Non-specific causes” The antibiotic causes death of the natural intestinal bacterial flora. This changes the mechanism in which organic compounds are broken down. This changes the mechanism in which organic compounds are broken down. Resulting in changes in the osmotic pressure within the lumen of the colon drawing fluid into the colon Resulting in changes in the osmotic pressure within the lumen of the colon drawing fluid into the colon Excess fluid changes the consistency and transit time of stool, producing diarrhea Excess fluid changes the consistency and transit time of stool, producing diarrhea

10. What is the theory driving the use of probiotics? Probiotics maintain the bacterial balance of the colonic flora. In turn inhibiting diarrhea related to bacterial as well as non-specific causes. Probiotics maintain the bacterial balance of the colonic flora. In turn inhibiting diarrhea related to bacterial as well as non-specific causes.

11. What are Probiotics? Life-viable, non-pathogen microbial organisms with 3 main properties: Life-viable, non-pathogen microbial organisms with 3 main properties: anti-inflammatory anti-viral anti-viralanti-bacterial (Meier, 2005)

12. Studies StudyProbiotic % of PROBIOTIC pts with diarrhea % of PLACEBO pts with diarrheaRiskReductionStudytype Hicks on et. al. Lactobacillus12%34%21.6% Randomi zed double blind placebo controlled Szajew ska et al. Saccharomyc es boulardii 6.7%17.2%10.5% Meta- analysis

13. Studies % of patients with AAD % of Patients in both Control and Placebo groups that experienced AAD

14. Studies Probiotic used Total # of studies included in review # of studies showing a significant decrease in AAD. # of studies showing no significant decrease in AAD Study type Hawrelak et. al. Lactobacillus642 Meta- analysis Johnston et. al. Lactobacilli spp., Bifidobacterium spp., Streptococcus spp., as well as Saccharomyces boulardii 1091 Meta- analysis Studies

15. # of Studies Meta-Analysis Number of studies within each Meta-Analysis that showed or failed to show a significant decrease in AAD with Probiotic use

16. Trend Three out of the four studies concluded that there was a significant decrease in AAD with probiotic use. Three out of the four studies concluded that there was a significant decrease in AAD with probiotic use. The fourth study concluded that further research was necessary to determine the role of probiotics in AAD. The fourth study concluded that further research was necessary to determine the role of probiotics in AAD.

17. Problems LACK of HOMGENICITY LACK of HOMGENICITY Age Age Type of antibiotic used Type of antibiotic used Strain of probiotic used Strain of probiotic used Length of antibiotic and probiotic treatment Length of antibiotic and probiotic treatment

18. Ages included in each study StudyAge Hickson et. al. >50 years Szajewska et al. 0 to >90 years Hawrelak et. al. 2 weeks to 93 years Johnston et. al. 0-18 years

19. Why not? If there is an obvious trend toward a decrease in AAD with probiotic use and these studies have been done in patients of all ages why not treat? If there is an obvious trend toward a decrease in AAD with probiotic use and these studies have been done in patients of all ages why not treat? None of the studies reported any adverse side effects. None of the studies reported any adverse side effects.

20. Risks Immunocompermised patients can become septic due to the introduction of probiotics. Immunocompermised patients can become septic due to the introduction of probiotics. There have been no reported cases of sepsis in a “otherwise healthy individual” There have been no reported cases of sepsis in a “otherwise healthy individual” (Boyle, 2006).

21. Conclusion Similar to all other clinical decisions, this is a matter of weighing the potential pros and cons. Similar to all other clinical decisions, this is a matter of weighing the potential pros and cons. While there is a obvious trend in the research before guidelines can be made further studies need to be done analyzing specific strains of probiotics, patient population, as well as antibiotic types and length of treatment. While there is a obvious trend in the research before guidelines can be made further studies need to be done analyzing specific strains of probiotics, patient population, as well as antibiotic types and length of treatment.

22. References Hickson, M., D'Souza, A.L., Muthu, N., Rogers, T.R., Want, S., & Chakravarthi, R. (2007). Use of probiotic Lactobacillus preparation to prevent diarrhoea associated with antibiotics: randomized double blind placebo controlled trial. BMJ, 335, 80. Hickson, M., D'Souza, A.L., Muthu, N., Rogers, T.R., Want, S., & Chakravarthi, R. (2007). Use of probiotic Lactobacillus preparation to prevent diarrhoea associated with antibiotics: randomized double blind placebo controlled trial. BMJ, 335, 80. Szajewska, H., & Mrukowicz, J. (2005). Meta-analysis: non-pathogenic yeast Saccharomyces boulardii in the prevention of antibiotic-associtaed diarrhoea. Aliment Pharmacology & Theraputics, 22, 365-372. Szajewska, H., & Mrukowicz, J. (2005). Meta-analysis: non-pathogenic yeast Saccharomyces boulardii in the prevention of antibiotic-associtaed diarrhoea. Aliment Pharmacology & Theraputics, 22, 365-372. Boyle, R.J., Robins-Browne, R.M., & Tang, M.L. (2006). Probiotic use in clinical practice: what are the risks?. The American Journal of Clinical Nutrition, 83, 1256-1264. Boyle, R.J., Robins-Browne, R.M., & Tang, M.L. (2006). Probiotic use in clinical practice: what are the risks?. The American Journal of Clinical Nutrition, 83, 1256-1264. Meier, Remy F. (2005).Probiotics: A New Treatment for Antibiotic- Associated Diarrhea?. Digestion. 72, 49-50. Meier, Remy F. (2005).Probiotics: A New Treatment for Antibiotic- Associated Diarrhea?. Digestion. 72, 49-50.