After the most exhaustive analysis to date on the efficacy of probiotics in preventing Clostridium difficile infection, a researcher recommends that high-risk patients consider taking the products.
Indeed, he takes exception to the current CDC position that there are not enough data to recommend the use of probiotics as prophylaxis against onset of C. diff infection (CDI).
“Are we withholding treatment from patients for something that looks to be safe and is generally inexpensive?” says Bradley Johnston, PhD, associate professor of epidemiology at Dalhousie University in Halifax, Nova Scotia.
“Are we withholding treatment from patients because we are too busy trying to figure out maybe this probiotic is slightly better than that one?”
Johnston is the co-author of two recent papers on probiotics, a Cochrane Review,1 and a new meta-analysis2 that looked at data on thousands of patients.
The CDC currently has “no recommendation” regarding probiotics, meaning they are neither endorsed nor contraindicated.
As the CDC epidemiologist Cliff McDonald, MD, recently told Hospital Infection Control & Prevention, “there is no single probiotic formulation that has been studied sufficiently to make a guide recommendation to use this probiotic in this dose for this period of time in these patients to prevent C. diff.”
However, Johnston says the accumulating evidence may be nearing a tipping point.
“I totally understand what he is saying, and it is an argument that is used a lot in the field,” he says.
“I disagree with it based on the data that was provided in the Cochrane review and now in this individual patient meta-analysis.”
In both reviews, Johnston and colleagues performed a subgroup analysis, looking to see if there were differences between the probiotics that have been studied.
“We found no difference among probiotic products,” he says.
“We did find a difference between multi-strain and single strain. But we can’t say, for example, one bacillus strain is better than another. There is no statistically significant difference. So, if that is case, this argument that we don’t know which product to use is very problematic.”
Thus, Johnston errs on the side of offering patients probiotics, particularly those that are at higher risk to an ongoing C. diff outbreak or on two or more antibiotics.
As IPs are aware, antibiotics can disrupt the gut bacterial balance, clearing the way for C. diff to set up and cause an infection.
Thus, the concept is that ingesting probiotics — living bacteria or yeast favorable to gut health — may reduce the risk of colonization with the pathogen. While that makes intuitive sense, proving it definitively in clinical medicine has been difficult, explaining in part the CDC’s neutral stance on probiotics.
Adding considerably to the evidence is Johnston’s most recent paper, which collected and analyzed data from 6,851 patients from 18 randomized trials of probiotics in nine countries. The number of patient records reviewed represents 79% of the 8,713 participants in the randomized trials.
Q & A
To further clarify the findings, Johnston agreed to the following interview with HIC.
HIC: What does this study add to the existing knowledge base on probiotics and C. diff?
Johnston: Two things. We found that those who received two or more antibiotic courses were more likely to benefit from probiotics.
In addition, those that received multispecies probiotics had more benefit than those that received a single species.
HIC: So, probiotics may have a benefit for patients on two or more antibiotics, particularly if the product they ingest has multiple bacillus strains?
Johnston: I don’t want to get carried away and suggest that probiotics are a magic bullet. They’re not. The largest randomized trial published in the Lancet3 several years ago showed that probiotics didn’t work. There was no significant effect, and why is that?
We think it is because the baseline risk [of acquiring CDI] in the study population was very low. The baseline risk was 1.2%, and they were not able to find a difference in patients with a risk that low.
We found that probiotics work better when there is a higher baseline risk [in patients]. If the baseline risk is 1.6%, 1.8%, or 2.1%, probiotics appear to be effective. They are much more effective when the baseline risk is high.
One of the take-home messages is that in a [C. diff] outbreak setting in a hospital, probiotics should be closely considered for use.
If a hospital is operating at a very low baseline risk — less than 1.5% — one might question whether they should have probiotics on their formulary and be recommending them for patients.
HIC: You talk about a two-thirds risk reduction, but conclude that to prevent one CDI case you need to give 96 patients probiotics. Can you explain?
Johnston: We know that multi-strain probiotics are more effective, and they are effective in patients that receive about two or more antibiotic scripts. And we know that they are more effective the higher the baseline risks.
If the risk is above 5%, the number needed to treat [a case] is about 12. If the risk is average across all studies — which is 1.6% — the number to treat is 96.
When we say a risk reduction of about two-thirds, that is a relative reduction risk compared to the control groups that have been observed.
We talk about data as relative numbers and absolute numbers, and ideally, we should always include both to the media and patients.
We should explain the difference between absolute and relative so they can make better decisions. The relative effects always sound more appealing and the absolute effects less so.
When I say, “You have to treat 96 patients in order to prevent one case of CDI,” it doesn’t sound overly compelling. If I say a two-thirds reduction, people say, “I’ll take it.”
- Johnston, B, Lytvyn L, Lo C, et al. Microbial Preparations (Probiotics) for the Prevention of Clostridium difficile Infection in Adults and Children: An Individual Patient Data Meta-analysis of 6,851 Participants. Infect Control Hosp Epi 1-11. 26 April 2018. DOI: 10.1017/ice.2018.84.
- Goldenberg JZ, Yap C, Lytvyn L, et al. Probiotics for the prevention of Clostridium difficile associated diarrhea in adults and children. Cochrane Database of Systematic Reviews 2017; 12: DOI: 10.1002/14651858.CD006095.pub4.
- Allen SJ, Wareham K, Wang D, et al. Lactobacilli and bifidobacteria in the prevention of antibiotic-associated diarrhoea and Clostridium difficile diarrhoea in older inpatients (PLACIDE): a randomised, double-blind, placebo-controlled, multicentre trial. Lancet 2013;382:1249–1257.
