Probiotics Keep C difficile at Bay in Patients on Antibiotics

Caroline Helwick

May 24, 2016

SAN DIEGO — For hospitalized patients receiving antibiotics, probiotics can protect against Clostridium difficile infection, a new meta-analysis shows.

"The available evidence strongly suggests that probiotics are safe and effective. They reduce the risk of C difficile in hospitalized patients taking antibiotics by more than 50%," said Nicole Shen, MD, an internal medicine resident at the New York Presbyterian–Weill Cornell Medical Center in New York City.

Morbidity and mortality related to C difficile infection is a billion-dollar problem. Prevention in those at high risk for infection is essential, but probiotics have been "inconsistently recommended," said Dr Shen.

"We thought, 'Why are we not using them?' This is where the inspiration for our study came from," she told Medscape Medical News.

Dr Shen presented the study results here at Digestive Disease Week 2016.

Previous systematic reviews and meta-analyses have shown probiotics to be protective, but they did not include PLACIDE, the largest randomized controlled trial of this approach (Lancet. 2013;382:1249-1257), she pointed out.

No protective effect of probiotics was shown in the almost 3000 patients evaluated in PLACIDE (relative risk, 0.70; P = .35); however, the study might have been underpowered because the incidence of C difficile infection in the control group was lower than expected, she explained.

Meta-analysis of 19 Studies

Dr Shen and her colleagues conducted a literature search and identified 19 studies published from 1989 to 2016 (including PLACIDE) that involved 6942 hospitalized adults taking antibiotics and receiving either a probiotic or placebo as prevention for C difficile infection. There was a significant difference in the incidence of infection between the probiotic and placebo groups (incidence, 1.5% vs 3.5%).

This represents an absolute risk reduction of 2% and a number needed to treat of 50 to prevent one infection, Dr Shen reported.

The pooled results show "robust efficacy" for probiotics in the prevention of C difficile infection (risk ratio, 0.41; 95% confidence interval, 0.30 - 0.57; P < .001). The greatest probiotic efficacy was seen in studies with the highest incidence of infection.

Prespecified subgroup analyses revealed no differences in probiotic species, strain, formulation, or dose, but did demonstrate that the timing of probiotic administration is important, said Dr Shen.

The overall relative risk for infection was 0.41, but when the probiotic was given within 2 days of the first antibiotic dose, the risk decreased to 0.32. When given beyond 2 days, the risk reduction was significantly lower (0.70; P = .02). Dr Shen pointed out that in the negative PLACIDE study, some patients received probiotics beyond 2 days.

There have been case reports of possible probiotic-associated sepsis, but none were reported in the studies evaluated in the meta-analysis. Adverse events were similar in patients treated with placebo and those treated with probiotics (relative risk, 0.97).

More studies are needed to identify optimal dose, treatment duration, and strains; however, Dr Shen said she personally recommends Saccharomyces boulardi and Lactobacillus GG (mixed strains).

Probiotics are most cost-effective in people 65 years and older, she added, which is the population at high risk for infection and poor outcomes after infection.

The findings from this meta-analysis are specific to immunocompetent hospitalized patients, she emphasized. Many of the studies excluded immunocompromised patients; some even excluded patients with inflammatory bowel disease. Ironically, this is a population that frequently takes probiotics, Dr Shen pointed out.

Most individuals can safely take these.

Patients with C difficile infection are often treated with fecal microbiota transplantation, but remain worried about recurrence, said Colleen Kelly, MD, assistant professor of medicine at the Brown University School of Medicine and a gastroenterologist at the Women's Medicine Collaborative in Providence, Rhode Island.

"They wonder what they can do to reduce their risk of recurrence when they need to take an antibiotic," she told Medscape Medical News. "The data on probiotics have been mixed. I think most would argue that the evidence is not the strongest, not coming from prospective clinical trials. But I think we have enough evidence now from this well-done meta-analysis that, for patients who can afford probiotics and are not immunocompromised, there's not really a downside."

She said she is cautious in severely immunocompromised patients, "but most individuals can safely take these."

Like Dr Shen, Dr Kelly recommends Saccharomyces boulardi and Lactobacillus GG. She emphasized that the brand should be "reputable," because quality controls in this industry are lacking.

Dr Shen and Dr Kelly have disclosed no relevant financial relationships.

Digestive Disease Week (DDW) 2016: Abstract 661. Presented May 23, 2016.


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