Probiotics to Prevent C. difficile Infections: Time for Clinical Recommendations?

Nicole Shen of New York-Presbyterian Hospital – Weill Cornell Medical Center and co-authors conducted an updated systematic review and meta-analysis on evidence for the efficacy of probiotics to prevent Clostridium difficile infection (CDI). They conducted this review for the stated purpose “…to help guide clinical practice.” To (mis)appropriate a line by Inigo Montoya in The Princess Bride, “You could not ask for a more noble cause than that.” It is noble to try, in an evidence-based manner, to close the gap that exists between data for probiotic efficacy and clinical implementation.

The study by Shen et al. evaluated data from 19 studies that tested if probiotics could prevent CDI in hospitalized adults taking antibiotics. They found that the relative risk of developing CDI was 0.42, the incidence of CDI in probiotic users was 1.6% compared to 3.9% among controls, and the number needed to treat (NNT) was 43 to prevent 1 case of CDI. Overall, the authors judged the quality of the evidence to be high, although 12 of the 19 included studies included one or two (of seven) criteria that were high risk of bias.

An important clinical observation made by the authors is that effectiveness increased when the probiotic was started soon after the first antibiotic dose. Also clinically important is that no increased risk for adverse events was associated with probiotic use.

Authors note that clarity is still needed regarding which probiotic formulations, dose and duration before precise clinical recommendations for probiotics to prevent CDI can be made. This is due to heterogeneity of these factors among included studies. Combining results on different probiotic strains and preparations into a single meta-analysis has been criticized, but legitimacy of the approach has also been discussed. The positive outcome from the Shen et al. analysis suggests that the ability to prevent CDI may be shared among the different probiotic species included (Lactobacillus, Saccharomyces, Bifidobacterium, and Streptococcus) and that several preparations may be effective.

The backdrop for this article is the morbidity and mortality resulting from CDI. A CDC report on the Burden of Clostridium difficile Infection in the United States estimated that in 2011 in the U.S. “C. difficile was responsible for almost half a million infections and was associated with approximately 29,000 deaths.” Importantly, CDI no longer seem restricted to acute care settings, such as hospitals and nursing homes. Appropriate antibiotic use and proper sanitation in acute care hospitals are associated with reducing CDI rates. But despite available evidence, medical guidelines do not currently recommend probiotics for prevention of CDI. Perhaps the conclusions from this Shen et al. study may start to change some minds.

 

Shen NT, Maw A, Tmanova LL, Pino A, Ancy K, Crawford CV, Simon MS, Evans AT. Timely use of Probiotics in Hospitalized Adults Prevents Clostridium difficile Infection: a Systematic Review with Meta-Regression Analysis. Gastroenterology. 2017, doi: 10.1053/j.gastro.2017.02.003.

See previous post:  Probiotics Fail to Impact Antibiotic Associated Diarrhea in Lancet Study  (August 2013)