Physicians consider probiotics for management of antibiotic-associated diarrhea

Prevention of diarrhea through judicious use of antibacterial agents and good infection control remains our best defense.

Issue: May 2006

ByMarianne Billeter, PharmD, BCPS

Diarrhea has been reported to occur with virtually all antibiotics on the market today.

The spectrum of diarrheal disease associated with antibiotic use ranges from frequent loose and watery stools with no other complications to colitis to toxic megacolon. Antibiotic-associated diarrhea occurs in about 2% to 10% of patients receiving antibiotic therapy. Clostridium difficile–associated disease accounts for 10% to 20% of cases of antibiotic-associated diarrhea. However, C. difficile accounts for most antibiotic–associated colitis. The incidence of antibiotic–associated diarrhea varies widely depending on the agents used. The β-lactam agents and clindamycin tend to have the highest rates of diarrhea with the macrolides and tetracyclines having the lowest rates. The quinolones are becoming increasingly important as a cause of C. difficile–associated diarrhea.

All across the United States, clinicians are reporting increasing numbers of C. difficile–associated diarrhea.

Marianne Billeter

Additionally, more severe disease with frequent recurrences and severe complications are also being reported. NAP 1, a new epidemic strain of C. difficile, is emerging and producing 16 times more toxin A and 23 times more toxin B than other strains. Treatment of C. difficile diarrhea includes metronidazole or oral vancomycin along with discontinuing the offending agent. With the increasing rate of recurrent disease, there is increasing interest in adjunctive treatment with probiotics.

Probiotics are nonpathogenic microorganisms that colonize the host and exert a positive effect on the health of the host after ingestion. Research has shown that the normal gut bacteria are a primary stimulus for normal intestinal immune system development and response. Probiotics may influence the immune interactions by suppressing the growth and attachment of potential pathogens.

The mechanism of probiotic action includes effects on luminal microecology, modulation of immune function and enhancement of gut barrier function. After ingestion, probiotics rapidly colonize the intestinal tract of the host. The lactic acid bacteria produce acetic, lactic and propionic acid, which lowers the pH in the lumen of the intestines. This, in turn, inhibits the growth of a wide variety of bacteria, including Clostridium. Additionally, four classes of bacteriocins are produced by lactobacilli. These are toxic to a relatively narrow spectrum of bacteria. Probiotics augment the intestinal immune system by a variety of mechanisms. They up-regulate and down-regulate the immune response following interactions with the epithelial cell lining of the intestinal tract. Probiotics have also been shown to alter intestinal mucus production and increase barrier function.

Weighing the evidence

Numerous microorganisms have been studied as probiotics for various gastrointestinal diseases. However, each individual microorganism exerts a different effect in the different diseases. Therefore, it is difficult to translate data from one microorganism to another. Lactobacillus rhamnosus GG and Saccharomyces boulardii are the most frequently studied probiotics for prevention and treatment of antibiotic-associated diarrhea, including C. difficile–associated diarrhea. Comparison of the studies is difficult because the studies use different definitions of antibiotic-associated diarrhea, different probiotic organisms, different doses of probiotic and different durations of follow-up. However, in general, the literature supports the use of both L. rhamnosus GG and S. boulardii in the prevention of antibiotic-associated diarrhea. However, no benefit was found in the prevention of C. difficile–associated diarrhea. The use of probiotics in the treatment of antibiotic-associated diarrhea, including C. difficile–associated diarrhea remains unproven. However, there are limited data to suggest a benefit of S. boulardii in preventing recurrent C. difficile diarrhea when used with the first recurrent episode.

There are numerous limitations to the studies using probiotics for management of antibiotic-associated diarrhea. First, for the probiotic to be effective, it must deliver viable organisms to the gastrointestinal tract. The available literature demonstrating whether the microorganisms are viable prior to ingestion and how many of the organisms remain viable following introduction to the gastric acid and in the basic environment of the intestinal lumen is lacking. Additionally, the antibacterial agents used to treat C. difficile–associated diarrhea may also have antibacterial effects on the probiotic, thus inhibiting the probiotic from rendering its positive effects.

The routine use of probiotics for the management of antibiotic-associated diarrhea and C. difficile–associated diarrhea cannot be recommended at this time. Prevention of antibiotic-associated diarrhea through the judicious use of antibacterial agents and good infection control procedures remains our best defense against this problem.

For more information:

Doron S, Gorbach SL. Probiotics: their role in the treatment and prevention of disease. Expert Rev Anti Infect Ther. 2006;4:261-275.

Novak J, Katz JA. Probiotics and prebiotics for gastrointestinal infections. Curr Infect Dis Rep. 2006;8:103-109.

Sunenshine RH, McDonald LC. Clostridium difficile-associated disease: new challenges from an established pathogen. Cleve Clin J Med. 2006;73:187-197.

Dendukuri N, Costa V, McGregor M, et al. Probiotic therapy for the prevention and treatment of Clostridium difficile-associated diarrhea: a systematic review. CMAJ. 2005;173:167-170.

D’Souza AL, Rajkumar C, Cooke J, Bulpitt CJ. Probiotics in prevention of antibiotic associated diarrhea: meta-analysis. BMJ. 2002;324:1361.