Probiotics fail the evidence triangle

I have heard seniors tell me about the use of probiotics in preventing antibiotic related complications like C.diff infection and diarrhoea. Sounds simple enough, theoretically sound, and supported by good evidence.

Several meta-analyses purported the benefits of probiotics:
Now, meta-analyses sit right at the top of the evidence triangle; the pinnacle of evidence based medicine. Or is it?

The authors of the JAMA article noted that while probiotics are associated with a reduction in antibiotic related diarrhoea, there exists significant heterogeneity in pooled results. Similarly, the Annals of Internal Medicine article also suffers from significant clinical heterogeneity as a limitation, a caveat rightly pointed out by the folks at

We all know that if you take a bunch of lousy studies and pool all the results together in a meta-analysis does not make the end result any better. Listen to the folk from SmartEM talk about thrombolytics in stroke and you'll get a fair idea.

A well conducted study, randomised controlled and properly blinded, will mostly provide a better answer. Thankfully, there is just that study done, the PLACIDE trial, recently published in Lancet 2013 Aug 8 (e-pub ahead of print).
In this UK study, 2941 older patients (age >65) who were about to start or recently were exposed to systemic antibiotics in five hospitals, were randomized to receive single capsules that contained either a multistrain preparation of Lactobacilli and Bifidobacteria, or placebo once daily for 21 days.

According to the accompanying editorial, the study was rigorous, there was central randomisation, with placebo control, good allocation concealment, and thorough follow-up was performed to identify antibiotic-related or C.diff diarrhoea. It was the largest trial to date to examine this topic in detail, the only fault of the trial being a lower than predicted event rate marring the confidence intervals.

It is then no wonder that the result of this RCT is actually negative for probiotics: the rate of antibiotic-related diarrhoea as well as C.diff diarrhoea were similar in the probiotic group versus the placebo group. So we can all say, at least in older patients > 65 years of age, probiotics given alongside antibiotic therapy, do not reduce the risk of antibiotic-related diarrhoea or C.diff diarrhoea.

For now, at least according to the Journal Watch reviewers, hand washing and antibiotic stewardship remains key.