9 Mar, 17 | by EBM
By Dr. Geoffrey Modest
A recent systematic review with a meta-analysis looked at 19 published studies on the efficacy of probiotics in preventing C. difficile infections (CDI) in inpatients put on antibiotics, finding benefit if given close to the 1st dose of antibiotics (see 10.1053/j.gastro.2017.02.003).
- 6261 subjects were involved in these 19 studies
- The studies were done in the USA, UK, Turkey, Canada, Norway, China, Italy, and Germany. Several different probiotic formulations were used, most with Lactobacillus species. The daily dose of probiotics varied dramatically from 4 to 900 colony forming units, most started the probiotics within the 1st 2 days of beginning the antibiotics, duration of probiotics varied from 14 days to 14 days after completion of the antibiotic course, and the age varied from those greater than 18 up to age 80 (weighted average 68 years). Commonly excluded groups were those who were pregnant, immunocompromised, required intensive care, had pre-existing GI disorders. The hospitals’ baseline incidence of CDI range from 1.5 to 7.4%
- Overall 4 probiotic species were studied: Lactobacillus, Saccharomyces, Bifidobacterium, and Streptococcus.
- The overall incidence of CDI in the probiotic cohort was 1.6% (54/3277); in the control group it was 3.9% (115/2984), with p<0.001.
- The pooled relative risk of CDI was decreased 58% with probiotics, RR 0.42 (0.30-.57)
- The number needed to treat was 43 patients to prevent one case of CDI
- Meta-regression analysis showed that there was a significant decline in probiotic efficacy for each day in delay of starting probiotics after the 1st dose of antibiotic, with an 18% decrease for every day the probiotics were delayed (p=0.04)
- Probiotics given within the 1st 2 days of starting antibiotics had a 68% risk reduction of CDI, RR 0.32 (0.22-0.48) than starting later, where there was a 30% reduction, RR 0.70 (0.40-1.23)
- No adverse events attributable to probiotics (in general adverse events tended to be less in the probiotic group)
- Overall quality of the evidence was high. The magnitude of efficacy was the same when analysis was limited only to the high qualities trials
- CDI incidence has increased dramatically in the past 10 years, more than doubling and costing $4.8 billion, with attendant morbidity and mortality (more than 29,000 deaths in 2011). The standard treatment has approximately 20% treatment failure and around half of the patients have recurrence, especially those who are older.
- Certain probiotics seem to colonize the gut well, despite concurrent use of antibiotics: specifically Lactobacillus and Bifidobacterium.
- To me it is difficult to assess with certainty their conclusions about timing, given the inconsistency of the approach to treatment (huge variability in types and doses of probiotics), as well as the fact that the vast majority of studies treated early, within the first 2 days or so. However, it does make intuitive sense that if we are to protect the gut with probiotics, that should be done early, especially before there is a large overgrowth of C. difficile
- The best guess of the authors, though not definitive, was at the most efficacious probiotics were: Lactobacillus, and Lactobacillus in combination with either Streptococcus or both Streptococcus and Bifidobacterium
- A review of the individual studies found that they all found benefit from the probiotics, though for some of the individual studies these did not reach statistical significance.
- A cost-benefit analysis done in the UK suggested that using a Lactobacillus probiotic in hospitalized patients over 65 on antibiotics would lead to a cost savings of over $500 per patient. Another study in Canada also suggested cost savings.
- So, though current guidelines, for example from the American College of Gastroenterology, do not recommend the use of probiotics for the primary prevention of CDI, this meta-analysis is pretty convincing that they work with no evident adverse effects. And, I would think, should be strongly considered in outpatients put on broad-spectrum antibiotics (e.g. Ciprofloxacin).
http://blogs.bmj.com/ebm/2014/12/03/primary-care-corner-with-geoffrey-modest-md-probiotics-in-irritable-bowel-syndrome/ is a blog on the efficacy of probiotics in irritable bowel syndrome
http://blogs.bmj.com/ebm/category/microbiome/ has a slew of blogs on the microbiome
http://blogs.bmj.com/ebm/category/clostridium-difficile/ has many blogs C. diff
and, http://blogs.bmj.com/ebm/category/antimicrobial-resistance/ has many on antimicrobial resistance