Key messages
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In people prescribed antibiotics, probiotics may be effective in preventing Clostridioides difficile-associated diarrhea (CDAD), and may reduce the risk of antibiotic-associated diarrhea.
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Probiotics probably do not result in harm when taken with an antibiotic, with fewer mild to moderate unwanted effects in the group receiving probiotic than the group receiving placebo (dummy treatment) or no treatment.
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In those taking antibiotics who do not have a weakened immune system, the short-term use of probiotics may offer a small benefit, and are likely not harmful. However, additional large studies comparing probiotics with placebo in people with a low risk of CDAD are needed.
What is Clostridioides difficile-associated diarrhea (CDAD)?
Antibiotics are among the most prescribed medications worldwide. Antibiotic treatment may disturb the balance of organisms that normally populate the gut. This can result in a range of symptoms, most notably diarrhea. C difficile is a particularly dangerous organism that may colonize and infect the gut if the microbial balance has been disrupted. The effects of C difficile infection can vary, with some people having no symptoms, and others suffering diarrhea, severe inflammation, enlargement of the colon, or even death. The cost of treatment is expensive, and the financial burden on the medical system is substantial.
What are probiotics?
Probiotics are live microorganisms (bacteria or yeast) that provide health benefits when given in adequate amounts. They help to prevent potential disturbances to the gut microbial balance that are associated with antibiotic use, and to reduce the risk of growing harmful bacteria. Probiotics can be found in dietary supplements or yogurts and are widely available as capsules sold in health food stores and supermarkets. As 'functional food' or 'good bacteria,' probiotics have been suggested as a means of both preventing and treating CDAD.
What did we want to find out?
We wanted to know if probiotics prevent CDAD in adults and children receiving antibiotic therapy, and whether probiotics cause any unwanted effects. The researchers searched the medical literature extensively up to 3 March 2025.
What did we do?
We searched for studies that compared probiotics (any strain or dose) versus placebo (dummy treatment), alternative preventive treatment, or no treatment for the prevention of CDAD in adults and children receiving antibiotic therapy for any reason. We compared and summarized the results of the studies and rated our confidence in the evidence based on factors such as study methods and sizes.
What did we find?
We included 47 studies with a total of 15,260 adults and children who received antibiotic therapy along with probiotics, assessing CDAD or C difficile growth. Thirty-eight studies (13,179 participants) assessed the effectiveness of probiotics for preventing CDAD. Our results suggest that probiotics may result in a small reduction in the risk of CDAD compared to placebo or no treatment.
Probiotics may result in a small reduction in C difficile growth (16 studies, 1302 participants). Thirty-seven studies (11,911 participants) looked at unwanted effects. Our results show that probiotics probably result in a small reduction in the risk of developing unwanted effects compared to placebo or no treatment. The most commonly reported unwanted effects included abdominal cramping, nausea, fever, soft stools, flatulence (gas), and taste disturbance, and were more common in the placebo or no-treatment group. Forty studies (13,419 participants) reported on antibiotic-associated diarrhea (AAD); probiotics may result in a large reduction in the risk of AAD compared to placebo or no treatment. Seven studies (6553 participants) reporting on length of hospital stay showed likely little to no difference between probiotics and placebo or no treatment.
What are the limitations of the evidence?
The studies we reviewed used different types of probiotics, but they didn't directly compare one probiotic to another. This lack of direct comparisons makes it harder to determine which probiotic works best.
We have moderate to little confidence in the available evidence. Our confidence is limited because in some studies, people who dropped out of the study or were not followed up on resulted in missing information. The two largest studies in our analysis did not show a clear benefit of probiotics for preventing CDAD.
How up-to-date is this evidence?
The evidence is current to 3 March 2025.
Read the full abstract
Antibiotics can disturb gastrointestinal microbiota which may lead to reduced resistance to pathogens such as Clostridium difficile (C. difficile). Probiotics are live microbial preparations that, when administered in adequate amounts, may confer a health benefit to the host, and are a potential C. difficile prevention strategy. Recent clinical practice guidelines do not recommend probiotic prophylaxis, even though probiotics have the highest quality evidence among cited prophylactic therapies.
Objectives
To assess the benefits and harms of probiotics for preventing C difficile-associated diarrhea (CDAD) in adults and children receiving an antibiotic for any reason.
Search strategy
We searched the Cochrane Central Register of Controlled Trials (CENTRAL), Ovid MEDLINE, and Ovid Embase from 18 March 2017 (search date of the previous version of the review) to 3 March 2025.
Selection criteria
Randomized controlled (placebo, alternative prophylaxis, or no treatment control) trials investigating probiotics (any strain, any dose) for prevention of CDAD, or C. difficile infection were considered for inclusion.
Data collection and analysis
Two authors (independently and in duplicate) extracted data and assessed risk of bias. The primary outcome was the incidence of CDAD. Secondary outcomes included detection of C. difficile infection in stool, adverse events, antibiotic-associated diarrhea (AAD) and length of hospital stay. Dichotomous outcomes (e.g. incidence of CDAD) were pooled using a random-effects model to calculate the risk ratio (RR) and corresponding 95% confidence interval (95% CI). We calculated the number needed to treat for an additional beneficial outcome (NNTB) where appropriate. Continuous outcomes (e.g. length of hospital stay) were pooled using a random-effects model to calculate the mean difference and corresponding 95% CI. Sensitivity analyses were conducted to explore the impact of missing data on efficacy and safety outcomes. For the sensitivity analyses, we assumed that the event rate for those participants in the control group who had missing data was the same as the event rate for those participants in the control group who were successfully followed. For the probiotic group, we calculated effects using the following assumed ratios of event rates in those with missing data in comparison to those successfully followed: 1.5:1, 2:1, 3:1, and 5:1. To explore possible explanations for heterogeneity, a priori subgroup analyses were conducted on probiotic species, dose, adult versus pediatric population, and risk of bias as well as a post hoc subgroup analysis on baseline risk of CDAD (low 0% to 2%; moderate 3% to 5%; high > 5%). The overall quality of the evidence supporting each outcome was independently assessed using the GRADE criteria.
Main results
Thirty-nine studies (9955 participants) met the eligibility requirements for our review. Overall, 27 studies were rated as either high or unclear risk of bias. A complete case analysis (i.e. participants who completed the study) among trials investigating CDAD (31 trials, 8672 participants) suggests that probiotics reduce the risk of CDAD by 60%. The incidence of CDAD was 1.5% (70/4525) in the probiotic group compared to 4.0% (164/4147) in the placebo or no treatment control group (RR 0.40, 95% CI 0.30 to 0.52; GRADE = moderate). Twenty-two of 31 trials had missing CDAD data ranging from 2% to 45%. Our complete case CDAD results proved robust to sensitivity analyses of plausible and worst-plausible assumptions regarding missing outcome data and results were similar whether considering subgroups of trials in adults versus children, inpatients versus outpatients, different probiotic species, lower versus higher doses of probiotics, or studies at high versus low risk of bias. However, in a post hoc analysis, we did observe a subgroup effect with respect to baseline risk of developing CDAD. Trials with a baseline CDAD risk of 0% to 2% and 3% to 5% did not show any difference in risk but trials enrolling participants with a baseline risk of > 5% for developing CDAD demonstrated a large 70% risk reduction (interaction P value = 0.01). Among studies with a baseline risk > 5%, the incidence of CDAD in the probiotic group was 3.1% (43/1370) compared to 11.6% (126/1084) in the control group (13 trials, 2454 participants; RR 0.30, 95% CI 0.21 to 0.42; GRADE = moderate). With respect to detection of C. difficile in the stool pooled complete case results from 15 trials (1214 participants) did not show a reduction in infection rates. C. difficile infection was 15.5% (98/633) in the probiotics group compared to 17.0% (99/581) in the placebo or no treatment control group (RR 0.86, 95% CI 0.67 to 1.10; GRADE = moderate). Adverse events were assessed in 32 studies (8305 participants) and our pooled complete case analysis indicates probiotics reduce the risk of adverse events by 17% (RR 0.83, 95% CI 0.71 to 0.97; GRADE = very low). In both treatment and control groups the most common adverse events included abdominal cramping, nausea, fever, soft stools, flatulence, and taste disturbance.
Authors' conclusions
The currently available evidence suggests that probiotics may be effective for preventing CDAD, suggesting that for every 65 people taking probiotics, one case of CDAD may be prevented (number needed to treat for an additional beneficial outcome of 65, 95% CI 48 to 97). There are probably fewer adverse events in the probiotic group. The short-term use of probiotics may have a small absolute benefit, and is likely not associated with adverse effects when used in patient populations receiving systemic antibiotics who are not immunocompromised. Large trials comparing probiotics with placebo in people with a low baseline risk of CDAD are needed.
Funding
There was no source of funding for this update.
Registration
The original review was done in 2013 by Johnston and colleagues, for which the protocol was developed. We followed the methods specified in the 2017 review, while modifying the search strategy and risk of bias assessment for selective reporting for this update.
