Cochrane Database Syst Rev

Could probiotics reduce C. difficile-associated diarrhea risk?

September 16, 2025

Study details: This Cochrane systematic review included 47 randomized trials (N = 15,260) evaluating probiotics (any strain/dose) vs. placebo, alternative prophylaxis, or no treatment for C. difficile-associated diarrhea (CDAD) prevention in adults and children receiving antibiotics. Outcomes assessed were CDAD incidence, C. difficile colonization, adverse events, antibiotic-associated diarrhea (AAD), and hospital length of stay. Risk of bias and evidence certainty were rigorously evaluated using GRADE.

Results: Probiotics reduced CDAD incidence from 3.2% in controls to 1.6% in the treatment group, resulting in an absolute risk reduction (ARR) of 1.6% and a relative risk (RR) reduction of 50% (P<0.001). These findings held up under sensitivity analyses despite missing data in 27 of 38 trials. Probiotics also modestly reduced asymptomatic C. difficile colonization (absolute risk reduction [ARR], 2.1%; RR 0.87; 95% CI, 0.68–1.11; P=0.27; low-certainty evidence) and AAD (ARR, 9%; RRR, 33%). Adverse events were slightly lower with probiotics (ARR, 1.7%), with no serious safety signals.

Clinical impact: Probiotics may be considered for CDAD prevention in patients at moderate-to-high baseline risk (e.g., elderly, hospitalized, broad-spectrum antibiotic use), but routine use in low-risk populations isn’t supported. The benefit is modest and strain-specific efficacy remains uncertain. Short-term use appears safe in immunocompetent patients.

Source:

Esmaeilinezhad Z, et al. (2025, September 11). Cochrane Database Syst Rev. Probiotics for the prevention of Clostridioides difficile-associated diarrhea in adults and children. https://pubmed.ncbi.nlm.nih.gov/40931979/