Probiotics do not prevent diarrhoea caused by antibiotics in older people, study finds
Probiotic supplements do not reduce the incidence of diarrhoea in older people being treated with antibiotics, a study has found.
The findings raise questions about whether the policy to give probiotics routinely to patients taking antibiotics, a policy being adopted by many hospitals, is a cost effective strategy, a commentator has said.
The prevention of antibiotic associated diarrhoea and Clostridium difficile diarrhoea in older inpatients (PLACIDE) study is a randomised controlled trial that was conducted in nearly 3000 patients aged 65 years and over being treated with at least one antibiotic in five hospitals in south Wales and northeast England.
Around half of the study participants were asked to take one capsule containing a fixed dose of live bacteria (two strains of Lactobacillus acidophilus, Bifidobacterium bifidum, and Bifidobacterium lactis) per day for 21 days, and between antibiotic doses where possible, while the other half received an identical placebo capsule, with the same dosing instructions.
The researchers analysed stool samples from around half of the patients who experienced diarrhoea to determine the cause of their symptoms, including Clostridium difficile.
They found that diarrhoea occurred in 10.8% of the patients given probiotics and was equally common (10.4%) in patients taking placebo (relative risk 10.04, 95% confidence interval 0.84-1.28; P=0.71). Diarrhoea caused by Clostridium difficile was uncommon and occurred in about 1% of the patients taking probiotics and those on placebo (relative risk 0.71, 0.34-1.47; P=0.35).
Stephen Allen, professor of paediatrics and international health at Swansea University, who led the study, said, Although some existing studies of the effect of probiotic supplements on AAD [antibiotic associated diarrhoea] have suggested that these supplements might effectively reduce the incidence of AAD, these results were based mostly on small trials conducted in single locations, many of which gave inconsistent results which are difficult to incorporate in meta-analyses.
Our study is by far the largest trial so far to assess the effects on AAD of so-called probiotics which might better be termed microbial preparations, given the uncertainty over whether they are indeed beneficial to health and the results do not support the use of these preparations to reduce rates of AAD in older inpatients.
However, he pointed out that a large number of possible bacteria may possess anti-diarrhoeal properties and these may warrant further investigation.
In an editorial on the trial Nick Daneman, of the Sunnybrook Health Sciences Centre, University of Toronto, Canada, pointed out that the PLACIDE trial is the largest trial to be reported in this discipline. Two recent meta-analyses have found that probiotics lead to large reductions in antibiotic associated diarrhoea and C difficile infections and have been motivating hospitals to adopt the routine probiotic administration alongside antibiotics. But these are based on small, single centre studies of variable quality.
He concluded: At the very least, the low absolute risk reductions in PLACIDE question the cost effectiveness of probiotics ¦PLACIDE is a large and rigorous negative study, and we must judge whether it can tip the balance of probiotic evidence.
- Allen SJ, Wareham K, Wang D, Bradley C, Hutchings H, Harris W, et al. Lactobacilli and bifidobacteria in the prevention of antibiotic-associated diarrhoea and Clostridium difficile diarrhoea in older patients (PLACIDE): a randomised, double-blind, placebo-controlled, multicentre trial. Lancet 8 Aug 2013, doi:10.1016/S0140-6736(13)
61218-0. [Free full-text Lancet article PDF | PubMed ® abstract]
- Daneman N. A probiotic trial: tipping the balance of evidence? Lancet 8 Aug 2013, doi:10.1016/S0140-6736(13)
61571-8. [Lancet article extract online | PubMed ® abstract]
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