MIAMI — Varying degrees of success and some caveats come with the use of probiotics to combat or prevent Clostridium difficile infection and antibiotic-associated diarrhea.

Saccharomyces boulardii, lactobacilli, and bifidobacteria are among the better-studied probiotic options for these purposes, Dr. Curtis Danskey said at the International Probiotics Association World Congress.

Many hospitalized patients do not have normal gut flora, but “if we can restore the normal intestinal flora, an effective probiotic may protect [these] patients,” said Dr. Danskey, who is on the medicine faculty at Louis Stokes Cleveland VA Medical Center.

C. difficile can cause up to 30% of nosocomial diarrhea cases in hospitalized patients (Pol. J. Microbiol. 2005;54:111–5). In addition, antibiotic-associated diarrhea (AAD) occurs in 3%–29% of hospitalized patients and is associated with increased length of stay and costs (J. Hosp. Infect. 2003;54:202–6).

The antibiotics routinely prescribed to fight C. difficile also kill beneficial flora in the gut, which is where probiotic therapy might help. “There is evidence [supporting the] use of probiotics for antibiotic-associated diarrhea if you want to use them,” Dr. Danskey said.

▸ Saccharomyces boulardii. This organism is a type of yeast and is “probably one of the most well-studied probiotics for C. difficile,” Dr. Danskey said. In one study, patients with C. difficile disease experienced a significant reduction in recurrences when treated with high-dose vancomycin for 10 days followed by S. boulardii for 28 days, compared with a regimen of vancomycin followed by placebo (Clin. Infect. Dis. 2000;31:1012–7).

On the downside, there have been several reports of fungemia associated with S. boulardii treatment, particularly in immunocompromised patients, Dr. Danskey said (Crit. Care 2008;12:414). There is a risk of transfer of fungemia to adjacent patients, so “I will not use it in my ICU, [but I] may use it in an outpatient setting in someone with recurrent infections,” he added.

▸ Lactobacilli and bifidobacteria. There is some rationale for use of these two probiotic species to prevent C. difficile infection, Dr. Danskey said. Lactobacilli, for example, can inhibit growth of C. difficile in vitro (J. Med. Microbiol. 2004;53:551–4). Also, reduced lactobacilli levels were found in the stool of hospitalized patients with C. difficile (Clin. Infect. Dis. 1997;25[suppl 2]:S189–90). “A lack of these organisms may allow C. difficile to grow.”

Historically, the numbers have been small in many probiotic trials that did not show a reduction in C. difficile infection. “Up to 2005, the data were not very convincing,” Dr. Danskey said.

After that, reports became more robust. For example, in one study, 135 hospitalized patients aged 50 years and older taking antibiotics were randomized to a lactobacillus preparation or placebo (BMJ 2007;335:80). A total of 12% of the probiotic group developed AAD, compared with 34% of placebo patients. In addition, no patient who took the probiotic developed a C. difficile infection vs. 17% of the placebo group.

“The results looked very impressive,” Dr. Danskey said. However, the study received a fair amount of criticism. For example, the placebo group drank a sterile milkshake, which could have caused diarrhea, some said. Other aspects of the study that drew criticism included the highly selected patient population (only 8% of screened patients were enrolled) and the exclusion of patients taking antibiotics most likely to cause diarrhea.

“However, the 8% rate is still higher than a just-published study [of monoclonal antibodies targeted against C. difficile toxins] that only enrolled 3% of screened patients,” Dr. Danskey said (N. Engl. J. Med. 2010;362:197–205). Also, in the 2007 lactobacillus study, 43 of 69 probiotic-treated patients (62%) received a high-risk antibiotic, as did 46 of the 66 placebo patients (70%), he said.

In terms of potential adverse events, there are some concerns about safety, “although we eat yogurt [with lactobacillus species] all the time,” Dr. Danskey said. For example, researchers reported two cases of sepsis associated with probiotic lactobacillus strains (Pediatrics 2005;115:178–810). He also cited a meta-analysis of the advantages and disadvantages of probiotics for AAD and C. difficile infection (Anaerobe 2009;15:274–80).

▸ Nontoxigenic probiotics. Normally, C. difficile growth and toxin production start shortly after infection in susceptible individuals. A person can be an asymptomatic carrier, but about one-third of patients develop disease, Dr. Danskey said. When this happens, C. difficile toxins bind to the lining of the GI tract, leading to cell death and significant inflammation. Colonoscopy and sigmoidoscopy often show pseudomembranous colitis in these patients.

Nontoxigenic probiotics that compete with C. difficile are in development. “Evidence suggests patients colonized with nontoxigenic strains were protected from infection with toxigenic strains,” Dr. Danskey said. “This makes logical sense—they will compete with toxigenic strains in the GI system.” So far, the evidence primarily comes from animal research. “It is now in phase I trials in patients and will move forward if it is shown to be effective and safe.”

Disclosures: Dr. Danskey receives research support from Viral Pharma (which is developing nontoxigenic probiotic strains) and the Department of Veterans Affairs.

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'There is evidence [supporting the] use of probiotics for antibiotic-associated diarrhea if you want to use them.'

Source DR. DANSKEY

Probiotics for C. difficile and Diarrhea Have Pros and Cons