By: Holly Sokol, PharmD Candidate 2020

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Antibiotic-associated diarrhea (AAD) can occur due to antibiotics changing the elements of the gut and thereby, increasing an organism’s inhabitance. Diarrhea is common in as many as 40% of critically ill patients. An even greater problem is Clostridium difficile (antibiotics-associated) becoming a leading cause of mortality in hospital-related infections.¹ Probiotics help prevent C. difficile infection in small scale studies; however, the results are still unclear in large-scale studies.¹

Studies have shown that probiotics are safe to use in AAD patients.² Probiotic use in AAD patients has increased with access to over-the-counter products.¹ After reviewing 16 studies and 3400 patients, a Cochrane Review determined Lactobacillus rhamnosus GG and S. boulardii to be effective probiotics in preventing ADD.³ In a single-center, randomized, double-blind, placebo-controlled dose-ranging study by Gao et al, hospitalized adult-patients were treated with a probiotic containing 50 billion colony-forming units of Lactobacillus.⁴ Patients that received two capsules daily had a lower incidence of AAD (15.5%)  than patients who received only one capsule (28.8%) or placebo (44.1%).⁴

1. difficle is a major cause of infectious diarrhea; overgrown bacteria release toxins that attack the lining of the intestines. Studies of probiotic use and C. difficle have shown inconsistent results. In a four-week randomized placebo-controlled trial after antibiotic therapy, S. boulardii (500 mg twice a day) reduced C. difficile-associated diarrhea (CDAD) recurrence rates.³ The objective of the study was to determine the safety and efficacy of a new combination treatment for patients with CDAD. Patients were randomized to S. boulardii or placebo after treatment with an antibiotic (vancomycin hydrochloride or metronidazole).⁵ Patients treated with S. boulardii had a significantly lower relative risk of CDAD recurrence (p=.04) compared with placebo (p=.86).⁵

However, there are several studies that fail to show benefit with probiotic treatment. The Placide study examined patients over the age of 65 who were not in an intensive care unit and who lacked a history of C. difficile infection. In the study, patients took two strains of Lactobacillus and two strains of bifidobacteria for 21 days through a microbial preparation. The patients were previous only oral or intravenous antibiotics. After eight weeks, there was no significant difference between the probiotic and placebo groups. While the medication was designed to make the patient better they received adverse side effects such as bloating (as an increase in 3-fold).¹ It is unclear if the solution is to bind the gut with another strain of bacteria.¹ In a systematic review, the efficacy of probiotic intervention in prevention of CDAD in older patients was evaluated. Among the six randomized control trials, 3562 patients 65 years or older were treated with various probiotic strains including Lactobacillus, Bifidobacterium, Saccharomyces, Streptococcus, Enterococcus and Bacillus.⁶ The systematic review found that none of the probiotics were effective in prevention of CDAD in older patients.

Due to the inconsistent results of trials, specialists feel probiotics are not completely effective. Paul Wischmeyer, MD, a critical care expert at the University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, believes the flaw was not the probiotic itself, but the way it was delivered.² After results from the PRObiotics in PAncreatitis TRIAl were publicized, in which probiotic bacteria was introduced in the small bowel and resulted in the death of eight people, data proved that probiotics should be distributed through the mouth and not directly through the gastrointestinal tract. Dr. Esaian, PharmD, BCPS, a pharmacotherapy specialist, critical care at the New York University Langone Medical Center, New York City, is hesitant to recommend probiotics to her critically ill patients because of the limited data available on agents.² Although results have varied, risk vs. benefit analysis ultimately depends on clinician practice and patient preferences.

 

SOURCES:

1. Johnson D. Probiotics: help or harm in antibiotic-associated diarrhea?. Medscape. http://www.medscape.com/viewarticle/830002#vp_3. Published 09/10/2014. Accessed 02/24/2015.
2. Rosenthal M. Probiotics for antibiotic-asssociated diarrhea in the ICU? Jury still out. pharmacypracticenews.http://www.pharmacypracticenews.com/ViewArticle.aspx?d=Web+Exclusives&d_id=239&i=January+2015&i_id=1141&a_id=29290. Published 01/21/2015. Accessed 02/24/2015.
3. Ciorba M. A gastroenterologist’s guide to probiotics. Medscape. http://www.medscape.com/viewarticle/770468_4. Published 10/09/2012. Accessed 03/28/2015
4. Gao XW, Mubasher M, Fang CY, Reifer C, Miller LE. Dose-response efficacy of a proprietary probiotic formula of Lactobacillus acidophilus CL1285 and Lactobacillus casei LBC80R for antibiotic-associated diarrhea and Clostridium difficile-associated diarrhea prophylaxis in adult patients. Am J Gastroenterol.2010;105(7):1636-41. doi: 10.1038/ajg.2010.11
5. McFarland LV, Surawicz CM, Greenberg RN, et al. A randomized placebo-controlled trial of Saccharomyces boulardii in combination with standard antibiotics for Clostridium difficile disease. JAMA.1994;271(24):1913-8.
6. Xie C, Li J, Wang K, Li Q, Chen D. Probiotics for the prevention of antibiotic-associated diarrhea in older patients: A systematic review. Travel Med Infect Dis.2015;13(2):128-134. doi: 10.1016/j.tmaid.2015.03.001

Published by Rho Chi Post