Low-Dose Oral Vancomycin Fails to Reduce C. diff Infections, Study Finds

A recent clinical trial led by researchers at the University of Wisconsin–Madison has revealed that low-dose oral vancomycin does not significantly reduce the recurrence of Clostridioides difficile (C. diff) infections among adults undergoing antibiotic therapy. The findings, published in the *JAMA Network Open* on July 7, 2025, indicate that while there was a lower recurrence rate among participants receiving vancomycin compared to those receiving a placebo, the difference was not statistically significant, with a recurrence rate of 43.6% versus 57.1% (absolute difference of -13.5 percentage points, 95% CI -35.1 to 8.0; P = .22).

The trial, titled "Oral Vancomycin for Prevention of Recurrent Clostridioides difficile Infection," aimed to assess whether administering 125 mg of oral vancomycin once daily could prevent recurrent C. diff infections in patients who had recently completed treatment for the infection. The study enrolled 81 adults from four health systems, including University of Wisconsin–Madison Health and Mayo Clinic, between 2018 and mid-2023. Participants were randomly assigned to receive either vancomycin or a lactose placebo throughout their antibiotic course and for five additional days post-treatment.

According to Dr. Julie A. Keating, the lead author of the study and a clinical researcher at the University of Wisconsin–Madison, the initial hypothesis was based on prior investigations suggesting vancomycin might hold potential benefits in preventing C. diff recurrence. However, recruitment challenges and the limited sample size of 81 participants ultimately left the study underpowered to conclusively determine the efficacy of the treatment. Nearly 40% of eligible patients declined to participate due to prior use of prophylactic vancomycin, while the COVID-19 pandemic further hindered participant accrual.

“Given the wide confidence intervals around the primary outcome and the non-significant P value, we cannot confirm nor refute the preventive effect of oral vancomycin,” Dr. Keating stated. Additionally, the study observed a concerning trend where participants receiving vancomycin exhibited increased colonization by vancomycin-resistant Enterococcus (VRE), with 50% of vancomycin recipients testing positive for VRE compared to 24% in the placebo group (P = .048).

Stuart H. Cohen, a professor of medicine and an expert in infectious diseases at the University of California, Davis, commented on the implications of the findings. He stated, “The study underscores the complexities of treating C. diff infections, particularly in patients receiving concurrent antibiotic therapy. While vancomycin is a cornerstone in treating C. diff, its role in prevention remains ambiguous.” Ultimately, the study highlights the need for further investigation into effective preventative strategies against C. diff, a bacterium known for its resilience and difficulty in eradication.

The findings from this trial may impact clinical practices regarding the use of vancomycin in preventing recurrent C. diff infections. Health professionals may need to reconsider the balance between effective treatment and the potential for increasing antibiotic resistance. Experts emphasize that future research should focus on larger, more robust trials to ascertain the true efficacy of interventions aimed at preventing C. diff recurrence.

In conclusion, while the trial led by the University of Wisconsin–Madison provides valuable insights into the challenges posed by recurrent C. diff infections, it also illustrates the complexities of antibiotic use in clinical settings and the pressing need for ongoing research to develop effective and safe preventive measures against these formidable infections.