Probiotics

Educational Objectives

The goal of this program is to review data about probiotics. After hearing and assimilating this program, the clinician will be better able to:

1. Explain the mechanisms of action of probiotics.

2. Review data about use of probiotics in the prevention of Clostridium difficile-associated diarrhea and the treatment of irritable bowel syndrome.

3. Recognize patients who may be at increased risk for adverse events with use of probiotics.

Summary

Introduction: in Canada, 2% to 25% of population experience antibiotic-associated diarrhea (often associated with macrolides with prokinetic effects [eg, erythromycin, amoxicillin-clavulanate]); recurrence rate of Clostridium difficile ≈20%; probiotics currently being investigated for prevention of, eg, necrotizing enterocolitis, atopic dermatitis, bacterial vaginosis (BV)

Probiotics and prebiotics: probiotics — healthy bacteria for gut; prebiotics — feed or nourish natural flora inside gut; eg, inulin (over-the-counter [OTC] fiber preparation), fructooligosaccharides (found in bananas); common probiotics — Bifidobacterium; Lactobacillus; Saccharomyces boulardii (yeast; first isolated from mangosteen and lychee fruits); when discussing probiotics for treating, eg, diarrhea, important to consider strain (eg, Lactobacillus rhamnosus GG [Culturelle] is strain of L rhamnosus)

Mechanisms of action: competition for binding sites — lactobacilli bind to intestinal epithelium to prevent other pathogenic bacteria from attaching; antibacterial actions — secretion of peroxidases by lactobacilli; vaginal insertion of lactobacilli-containing ovules (available OTC) effective for BV (conversion of lactose to lactic acid by lactobacilli decreases vaginal pH, thereby making environment inhospitable to pathogens); immune modulation — S boulardii shown to decrease proinflammatory mediators; in in vitro studies, S boulardii shown to degrade toxins A and B from C difficile; strengthening of intestinal barrier — some probiotics secrete mucin to form protective layer over intestines to stabilize tight junctions in intestines; metabolic functions — some probiotics can increase absorption of certain minerals and nutrients

Quality of evidence: randomized controlled trials investigating probiotics often have design flaws, issues in recording data, lack of information about type of probiotic or strain being studied, and poor reporting of population’s baseline characteristics

Meta-analyses: 2012 studies (one including 34 randomized controlled trials with NNT 8, and second looking at 63 randomized controlled trials with NNT 13) suggested that probiotics associated with reduction in antibiotic-associated diarrhea; studies primarily looked at Lactobacillus and S boulardii

Probiotic use in C difficile infections: 2008 meta-analysis — looked at 4 randomized controlled trials to determine whether probiotics can treat recurrence of C difficile infections; found that probiotics alone do not treat C difficile infections; decreased recurrence of C difficile infection seen in adults who received S boulardii in addition to antibiotic therapy (eg, vancomycin and metronidazole); S boulardii suggested for primary prevention, but evidence insufficient for treatment of secondary infections; 2012 meta-analysis — looked at 11 randomized controlled trials; primary prevention with use of probiotics decreased C difficile infections; subgroup meta-analysis looked at commonly commercially available combination of 2 Lactobacillus strains (in 3 randomized controlled trials, incidence of C difficile infections decreased [statistically significant]); second subgroup meta-analysis looked at S boulardii (findings not statistically significant, but decrease seen in trend; more studies needed); 2012 meta-analysis (Johnston et al) — looked at 20 randomized controlled trials; found probiotics associated with large reduction in C difficile-associated diarrhea (CDAD) without increase in clinically important adverse events (NNT ≈30); probiotics may be beneficial in decreasing C difficile infections, but wide spectrum used in studies (difficult to identify which specific genera beneficial); 2013 meta-analysis (Goldenberg et al) — looked at 23 randomized controlled trials; suggested that probiotics safe and effective for prevention of CDAD; study showed relative risk reduction of 64% in patients who used probiotics for C difficile infections, but risk reduction not as high in those with CDAD; Allen et al (2013) — multicenter, randomized, controlled placebo trial; saw no statistically significant difference in prevention of AAD or CDAD in geriatric population (negative result may be due to probiotic combination)

Probiotic use in irritable bowel syndrome (IBS): meta-analysis (2010) — looked at 19 randomized controlled trials; concluded that probiotics appear efficacious for global symptoms (eg, abdominal pain, bloating, flatulence); which specific genus appropriate remains unclear

Probiotic strains and clinical uses: IBS — Lactobacillus plantarum 299v (TuZen); Bifidobacterium infantis 35624 (Align); combination of Bifidobacterium, Lactobacillus, and Streptococcus strains (eg, VSL#3 [refrigerated product]); AAD — Lactobacillus reuteri (eg, BioGaia [refrigerated product]); S boulardii (eg, Florastor); Lactobacillus acidophilus and Lactobacillus casei (eg, Bio K+ [refrigerated product]); costs ≈$1/day

Safety of probiotic use: randomized controlled trials did not indicate any association with increased risk; long-term effects unknown (longest duration of studies 1.5-2.0 yr [showed safety]); probiotic use in patients with immune compromise, patients undergoing chemotherapy, and those with bowel damage (movement of probiotics over intestinal lining and into bloodstream can cause septicemia) may be associated with increased risk for serious events; however, some evidence supports use of probiotics in patients with HIV and those undergoing chemotherapy

Technology report by Agency for Healthcare Research and Quality: neither long-term nor short-term use of probiotics show widespread association with harm; when harm occurred, generally gastrointestinal in nature; in randomized controlled trials showing evidence of harm, strains not specified; summary — probiotics shown relatively safe; caution important in certain populations (eg, patients with bowel damage)

Conclusion: probiotics may be strain-specific; may be beneficial for AAD and IBS; short-term use not shown to increase frequency of adverse events

Readings

No authors listed: Canadian Task Force on Preventive Health Care. Recommendations on screening for breast cancer in average-risk women aged 40-74 years. CMAJ. 2011 Nov 22;183(17):1991-2001; Allen SJ et al: Lactobacilli and bifidobacteria in the prevention of antibiotic-associated diarrhoea and Clostridium difficile diarrhoea in older inpatients (PLACIDE): a randomised, double-blind, placebo-controlled, multicentre trial. Lancet. 2013 Oct 12;382(9900):1249-57; Brawley OW: How We Do Harm. New York, NY. St. Martin’s Press; 2011; Brawley OW: Risk-based mammography screening: an effort to maximize the benefits and minimize the harms. Ann Intern Med. 2012 May 1;156(9):662-3; Goldenberg JZ et al: Probiotics for the prevention of Clostridium difficile-associated diarrhea in adults and children. Cochrane Database Syst Rev. 2013 May 31;5:CD006095; Heleno B et al: Quantification of harms in cancer screening trials: literature review. BMJ. 2013 Sep 16;347:f5334; Hempel S et al: Probiotics for the prevention and treatment of antibiotic-associated diarrhea: a systematic review and meta-analysis. JAMA. 2012 May 9;307(18):1959-69; Johnson S et al: Is primary prevention of Clostridium difficile infection possible with specific probiotics? Int J Infect Dis. 2012 Nov;16(11):e786-92; Johnston BC et al: Probiotics for the prevention of Clostridium difficile-associated diarrhea: a systematic review and meta-analysis. Ann Intern Med. 2012 Dec 18;157(12):878-88; Krogsboll LT et al: General health checks in adults for reducing morbidity and mortality from disease: Cochrane systematic review and meta-analysis. BMJ. 2012 Nov 20;345:e7191; Moayyedi P et al: The efficacy of probiotics in the treatment of irritable bowel syndrome: a systematic review. Gut. 2010 Mar;59(3):325-32; McCartney M: Where’s the evidence for NHS health checks? BMJ. 2013 Oct 2;347:f5834; Nestle M: What to Eat. New York, NY. North Point Press; 2006; Ngwakongnwi E et al: Documentation of preventive screening interventions by general practitioners: a retrospective chart audit. BMC Fam Pract. 2010 Mar 9;11:21; Pillai A, Nelson R: Probiotics for treatment of Clostridium difficile-associated colitis in adults. Cochrane Database Syst Rev. 2008 Jan 23;(1):CD004611; Smith RA et al: Cancer screening in the United States, 2013: a review of current American Cancer Society guidelines, current issues in cancer screening, and new guidance on cervical cancer screening and lung cancer screening. CA Cancer J Clin. 2013 Mar-Apr;63(2):88-105; Videlock EJ, Cremonini F: Meta-analysis: probiotics in antibiotic-associated diarrhoea. Aliment Pharmacol Ther. 2012 Jun;35(12):1355-69.

Disclosures

In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty and members of the planning committee to disclose relevant financial relationships within the past 12 months that might create any personal conflicts of interest. Any identified conflicts were resolved to ensure that this educational activity promotes quality in health care and not a proprietary business or commercial interest. For this program, members of the faculty and planning committee reported nothing to disclose.

Acknowledgements

Dr. Tran was recorded in Calgary, AB, at the 38th Annual Family Practice Review and Update Course, presented November 18-21, 2013, by the University of Calgary Faculty of Medicine. Visit www.cme.ucalgary.ca for information about upcoming meetings from this sponsor. The Audio-Digest Foundation thanks Dr. Tran and the University of Calgary Faculty of Medicine for their cooperation in the production of this program.

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 0 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 0 CE contact hours.

Lecture ID:

FP621102

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.

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