Oral Vancomycin Linked to Lower Clostridioides difficile Recurrence but Raises VRE Concerns: JAMA
Researchers have found in a new randomized clinical trial that oral vancomycin reduced recurrent C. difficile infection (CDI) rates in patients taking antibiotics for non-CDI indications, though the study was underpowered to reach statistical significance. A significant difference in VRE (vancomycin-resistant enterococci) carriage was noted at 8 weeks, with VRE decreasing in the placebo group but not in the vancomycin group. The findings therefore emphasize the need to explore alternative interventions for preventing CDI recurrence. The study was published in JAMA by Julie A. and colleagues.
This study was performed in four major health systems in the Upper Midwest region of the United States. Adult participants who had completed treatment for CDI in the past 180 days and were being prescribed systemic antibiotics for unrelated infections were enrolled from May 21, 2018, through March 30, 2023. A total of 81 patients were randomized in a 1:1 ratio to receive either 125 mg of oral vancomycin once daily or a placebo, administered during the course of systemic antibiotic therapy plus 5 days post-antibiotic use. Participants were followed up for 8 weeks after completion of study treatment to determine recurrence and other outcomes.
Key Findings
• Of the 81 participants enrolled (median age 59 years, IQR 50–67 years), 39 were treated with oral vancomycin and 42 with placebo.
• Recurrent CDI developed in 17 participants (43.6%) in the vancomycin arm versus 24 participants (57.1%) in the placebo arm.
This created an absolute difference of -13.5% (95% CI, -35.1% to 8.0%), which was not statistically significant. 60 participants (74.1%) completed the 8-week follow-up:
• 31 from the vancomycin group and 29 from the placebo group.
• Adverse effects were frequent and affected 27 members in each group, representing 69.2% for the vancomycin arm and 64.3% for the placebo arm.
• As for antimicrobial resistance, vancomycin-resistant Enterococcus (VRE) stool colonization was found in 15 out of 30 members (50%) in the vancomycin arm but only in 6 out of 25 members (24%) in the placebo group (P = 0.048), which posed a concern about the development of resistance.
Overall, this multicenter randomized clinical trial indicated that oral vancomycin administered as prophylaxis with and after systemic antibiotic treatment might be related to lower recurrence of CDI, although the outcome failed to be statistically significant. Furthermore, vancomycin utilization was associated with greater carriage of vancomycin-resistant Enterococcus, the issue warranting serious consideration prior to routine prophylactic application. Larger, well-powered trials are needed to validate these results and completely determine the risk-benefit ratio of oral vancomycin prophylaxis for prevention of recurrent CDI.
Reference:
Keating JA, Xu T, Graham MB, et al. Oral Vancomycin for Prevention of Recurrent Clostridioides difficile Infection: A Randomized Clinical Trial. JAMA Netw Open. 2025;8(7):e2517834. doi:10.1001/jamanetworkopen.2025.17834
