Probiotics Cut Antibiotic-Associated C diff Diarrhea by 66%

Jenni Laidman

A meta-analysis of 20 trials covering 3800 participants found probiotics were associated with a 66% reduction in the incidence of Clostridium difficile–associated diarrhea (CDAD), according to a study published online November 13 in Annals of Internal Medicine.        

Bradley C. Johnston, PhD, postdoctoral fellow, The Hospital for Sick Children Research Institute, Toronto, Ontario, Canada, and colleagues say the study provides "moderate-quality evidence" favoring probiotic prophylaxis during antibiotic treatment. Probiotics were associated with a reduced CDAD incidence of 66% (pooled relative risk [RR], 0.34 [95% confidence interval (CI), 0.24 - 0.49]; I² = 0%) and corresponded to very few adverse events.

Probiotic prophylaxis would prevent 33 episodes of antibiotic-associated CDAD per 1000 patients, the authors report, with a relative risk for clinically relevant adverse events of 0.82 (CI, 0.65 - 1.05; I ²= 17%). Among probiotic-treated patients, 9.3% experienced adverse events compared with 12.6% of control patients.

"Moderate-quality evidence supports a large protective effect of probiotics in preventing CDAD," the authors write. "Given the low cost of probiotics and the moderate-quality evidence suggesting the absence of important adverse effects, there seems little reason not to encourage the use of probiotics in patients receiving antibiotics who are at appreciable risk for CDAD."

"It's pretty exciting stuff," Patricia L. Raymond, MD, associate professor, Eastern Virginia Medical School, Norfolk, told Medscape Medical News. Dr. Raymond was not associated with the study. "The studies [considered in the meta-analysis] all had different timing of [probiotic treatment] onset, using different probiotics at different doses — it was really a grab bag. But it didn't matter what you gave or how you gave it. Pool all the data, and it was still a decent thing to do."

Still, Dr. Raymond said, just how cost-effective probiotic treatment proves to be will depend on which probiotics are used and how vulnerable the patient might be to CDAD. "A 66% reduction is really exciting. Thirty-three cases in 1000 patients is kind of wimpy. That's 963 people who didn't need to take probiotics who took them."

Elizabeth J. Videlock, MD, a research fellow in medicine, Beth Israel Deaconess Medical Center, Boston, told Medscape Medical News that a meta-analysis she coauthored, published in April in Alimentary Pharmacology and Therapeutics, showed a similar effect in prevention of all types of antibiotic-associated diarrhea.

"We also had findings that supported a class effect rather than an effect of any specific probiotic strain," Dr. Videlock wrote in an email. "This would suggest that even less costly forms of probiotics than Culturelle or Florastor would benefit patients — i.e. yogurt on the trays. It's time to adopt this into practice instead of saying that we need better trials. There is enough evidence."

Dr. Johnston and colleagues note that in more than half of the trials in their study — 13 of the 20 — CDAD data were missing for 5% to 45% of patients, a study weakness. The authors also note their study sample size of 3818 was smaller than the optimal information size of 5676 people, leading the authors to judge the evidence in the study as "moderate."

All but 1 of the trials were blinded, and the trials used several probiotics in a variety of doses given at various times during the course of antibiotic administration.

It's well known that antibiotics can disturb the ability of normal gastrointestinal flora to resist pathogen colonization. Treatment with probiotics at some stage of antibiotic treatment is thought to reinoculate the gut's disturbed microflora.

Approximately a third of all cases of antibiotic-associated diarrhea are attributed to C difficile, especially among older, hospitalized adults, the authors report. Occurrence and severity of C difficile infection have increased in the last decade, with almost 300,000 hospital cases annually, the authors state, citing studies in the New England Journal of Medicine, The Lancet, and Emerging Infectious Diseases. Since 2002, CDAD-related deaths almost doubled in the United States.

Dr. Johnston has a grant or pending grant (money to institution) from Biocodex and was supported in part by a postdoctoral fellowship from the SickKids Foundation. A coauthor has a grant from and has received support for meeting travel from Bastyr Center for Student Research. Dr. Raymond and Dr. Videlock have disclosed no relevant financial relationships.

Ann Intern Med. Published online November 13, 2012. Abstract