Probiotics: Their Role in Medicine Today Viki Barr Pharm.D., BCPS AQ ID Assistant Professor, Pharmacy Practice Rosalind Franklin University of Medicine and Science Clinical Pharmacist, Infectious Diseases Northwestern Memorial Hospital The speaker has no conflicts of interests to disclose Objectives Identify potential advantages and disadvantages of probiotics Describe the potential roles that probiotics play in therapy today, particularly prophylaxis for Clostridium difficille (C.diff) Identify differences between some of the current probiotics used for the prevention of Clostridium difficille Probiotics: What Are They? Per WHO they are: Live microorganisms which when administered in adequate amounts confer a health benefit on the host Can be a single or multiple bacterial or fungal strains Microbial species that have been shown in controlled studies to confer benefits to health Hill, C et al. Nat Rev Gastro Hepatol. 2014(11);506 514. 1
Probiotics Lactobacillus spp. acidophilus brevis casei curvatis fermentum rhamnosus reuteri salivarius Sacharomyces boulardii Bifidobacterium spp. bifidum breve infantis lactis longum Other Bacillus subtillis Enterococcus faecalis Streptococcus spp. Probiotic Proposed Uses Antibiotic associated diarrhea, infectious diarrhea, C.difficile IBS and IBD Recurrent UTI s Immune system enhancement H. pylori infections Dental carries Constipation Pediatrics Flock MH, et al. J Clin Gastro 2011;45;S168 S171 Clostridium difficile Gram positive spore forming anaerobic bacilli Colonization via fecal oral route Capable of producing toxins Toxin A enterotoxin Toxin B cytotoxin essential for virulence In 2003, emergence of NAP1/BI/027 which is the hypervirulent strain Associated with outbreaks Approximately 500,000 cases a year 25% recurrence 2
Cycle of C. difficile Infection https://www.bcm.edu/research/labs/robert britton/research areas/intestinal bacteria. Reprinted with permission, 10/2017, How Do Probiotics Work? Many probiotics can easily make it to the lower gut Ex. L. acidophilus Tolerated low ph just fine Detectible in feces Occasionally detectable at extra intestinal sites These organisms are usually selected because they are resistant to antibiotics used Probiotic Proposed Mechanism for C.difficile Competition for essential nutrients Production of antimicrobial factors Provide favorable environment for growth of other beneficial bacteria Adhere and stimulate gut immune system Up regulation of mucin gene Alter gut ph Enhance secretory IgA Hill, C et al. Nat Rev Gastro Hepatol. 2014(11);506 514. 3
Probiotic Uses Prophylaxis Primary and secondary Primary C. difficille infections vs. recurrent C. difficille Treatment Adjunctive or primary C. difficille infection vs. antibiotic associated diarrhea Primary Prevention of C. difficile Meta analysis Analyzed data from 19 published RCT studies Comprising 6261 subjects Primary Outcome Incidence of Clostridium difficile infection Secondary Outcome Incidence of adverse effects Secondary analyses examined the effects of probiotic species, dose, timing, formulation, duration, and study quality Shen NT, et al. Gastroenterologyl. 2017;152(8);1889 1900. Primary Prevention of C. difficile The incidence of CDI in the probiotic cohort, 1.6% (54 of 3277), was lower than of controls 3.9% (115 of 2984) (P <.001). The pooled relative risk of CDI in probiotic users was 0.42 (95% confidence interval, 0.30 0.57) Shen NT, et al. Gastroenterologyl. 2017;152(8);1889 1900. 4
Primary Prevention of C. difficile Meta regression analysis demonstrated probiotics were more effective if given closer to day 1 of antibiotics Decreasing efficacy for every day of delay in starting probiotics (P =.04) Shen NT, et al. Gastroenterologyl. 2017;152(8);1889 1900. Primary Prevention of C. difficile Study concluded that they found evidence that administration of probiotics closer to the first dose of antibiotic reduces the risk of CDI by >50% in hospitalized adults Future studies need to be concluded to focus on: Optimal dose Species Formulation Shen NT, et al. Gastroenterologyl. 2017;152(8);1889 1900. Are Probiotics Safe? Unregulated Bacteremia, fungemia and endocarditis reports Increased mortality in acute pancreatitis Long term complications? Microbiota is associated with many conditions Hammerman C, et al. BMJ. 2006;333;1006 1008. Besselink MG, et al. The Lancet. 2008;371(9613);651 659. 5
Who Should Not Receive Probiotics? Patients with indwelling lines Patients with short gut syndrome Critically ill patients in ICU s Suspected acute pancreatitis Immunocompromised patients On chemotherapy Untreated HIV Recent Transplant Hammerman C, et al. BMJ. 2006;333;1006 1008. So Which Probiotic to Choose? Safety and efficacy varies by strain Mostly safe as long as no risk factors in host identified Many suboptimal efficacy studies A Guidelines and Consensus http://scienceofprobiotics.ca/wp content/uploads/2015/01/probiotic Chart 2014.pdf 6
Adult Recommendations Use Prevention of Antibiotic Associated Diarrhea (AAD) Prevention of Clostridium Difficile Associated Diarrhea (CDAD) Brand name BioK+ BioGaia Culturelle Florastor GoodBelly NatureMade UltraFlora BioK+ Florastor GoodBelly Nature Made UltraFlora Conclusion Probiotics are generally safe (some exceptions) and well tolerated Lack of regulation When used for prevention of C. difficile must be given within first 1 2 days of antibiotic use Need for more data on strain type used since this is likely to matter Assessment Questions What is potential disadvantage of a probiotics? A. They are unregulated by the FDA B. They have a potential risk of bacteremia C. Immunocompromised individuals highly at risk for C.difficile infections are not ideal candidates for probiotics. D. All the above 7
Assessment Questions What is a potential role that probiotics play in therapy today, in regards to Clostridium difficille? A. May be used for prevention of C.difficile infection if started with a course of antibiotics B. Can be used as sole treatment of C.difficile C. There is no use of probiotics for C.difficile infections Assessment Question Which of the following statements is TRUE: A. All commercially available probiotics contain the same live microorganism strain B. Probiotics cannot be compared to one another C. Culturelle brand can be used for both prevention of AAD and for CDAD D. All probiotics work in the same location within the gut 8