C. difficile infection is a disease of dysbiosis – the most common pathology is that antibacterial agents disturb the balance of micro-organisms in the gut leaving C. difficle the ecological space to produce toxin and cause diseases. So, could it be that ‘probiotics’ could fill the ecological space and reduce the risk of CDI? Despite numerous trials, the jury is out!
I was asked by a senior colleague to explain why we are not giving a shot of probiotic yoghurt with each does of antibacterial agent, based on this study. The study is in many ways impressive: a multi-centre double blind placebo controlled trial. Patients who were prescribed certain antibacterial agents were enrolled and randomised to either live probiotic yoghurt or ‘sterile’ placebo control, in similar packaging. Both diarrhoea and C. difficile toxin-positive infection were significantly lower in the intervention group (12% vs. 34% for diarrhoea, and 0% vs. 9% for C. diffiicle toxin). Multi-variable logistic regression was performed only for diarrhoea, and showed that treatment remained a significant variable when accounting for other patient-level variables.
The study has two major limitations. First, the exclusion criteria were very stringent, meaning that only 135 of 1760 patients that were approached were enrolled. This raises questions about how generalizable the study population is. Second, patients who had received a ‘high-risk antibiotic’ were excluded (due to the risk of previous antibiotic-associated diarrhoea), meaning that the study group were at a lower risk of antibiotic-associated diarrhoea in the first place. I have been involved in a study previously that was criticised heavily for having exclusion criteria that were too tight, and I can’t begin to tell you how annoying it is, so I have some sympathy for the authors.
I think it’s fair to say that the majority of cases of CDI are not due in-hospital cross-transmission (although many are). This argues for prevention strategies aimed at the individual rather than the population. A 2013 Cochrane review concludes that there is ‘moderate’ evidence that probiotics prevent CDI, so perhaps this is an individual prevention strategy that we should think seriously about implementing.