Effectiveness of Oral Vancomycin in Preventing C diff Remains Uncertain after Trial

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The role of oral vancomycin in preventing recurrence of C difficile infection (CDI) in at-risk persons receiving systemic antibiotic for non-CDI infection remains unclear after randomized trial.

Vancomycin-resistant Enterococcus (VRE) Enterococcus faecalis is a type of bacteria that is resistant to vancomycin

Vancomycin-resistant Enterococcus (VRE) Enterococcus faecalis is a type of bacteria that is resistant to vancomycin

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Adding oral vancomycin to a systemic antibiotic treatment of a non- Clostridioides difficile infection (CDI) to prevent CDI recurrence in at-risk patients was associated with a lower rate of recurrence than in those not receiving vancomycin in a placebo-controlled trial1, but the difference was not statistically significant and the rates were high in both groups.

"Interventions to prevent recurrent CDI during exposure to systemic antibiotics in a person with prior but not current CDI are needed in clinical practice." Julie Keating, PhD, Department of Medicine, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin, and colleagues indicated.

Although the study was underpowered due to challenges in recruiting participants, the investigators found the lack of clear advantage suggested "that other interventions should be investigated for their effectiveness in preventing CDI recurrence after non-CDI-indicated antibiotic therapy".

Keating and colleagues recruited 81 participants with a documented diagnosis of 1 or more CDIs within the past 180 days; completion of a CDI treatment; and receiving non-CDI-indicated systemic antibiotics for 2 weeks or less and not more than 72 hours at enrollment. The vancomycin group received 125mg orally daily during, and for 5 days after their systemic antibiotic regimen while the control group received placebo in identical capsules. Recruitment challenges, including lack of interest in those with history of CDI to potentially receive placebo, left the size of the cohort one less than the minimum calculated to adequately power the study.

With that limitation on drawing conclusions, the investigators reported CDI recurred in 17 of 39 participants ( 43.6%) in the vancomycin group over the 8 week post-treatment follow-up period compared to 24 of 42 in the placebo group (57.1%). There was a statistically significantly higher rate of carriage of vancomycin-resistant Enterococcus (VRE) detected in the gut of those receiving vancomycin (15 of 30, 50%) than those without vancomycin exposure (6 of 25, 24.0%).

In accompanying commentary2, Stuart Cohen, MD, Division of Infectious Diseases, Department of Internal Medicine, University of California Davis School of Medicine, Davis, California, remarked that while the difference in rate of CDI recurrence between the groups was numerical rather than statistically significant, "the reduction appears to be a clinically meaningful result."

"What is striking, however, is how high the rates of recurrence were in both the treatment (43.6%) and placebo (57.1%) groups," he observed.

What You Need To Know

Oral vancomycin given alongside systemic antibiotics showed a lower, but not statistically significant, recurrence rate of CDI in high-risk patients.

The vancomycin group had significantly higher rates of VRE colonization, raising concerns about unintended microbial consequences.

Due to high recurrence rates in both groups and study limitations, further research is needed to explore more effective and safer preventive strategies for recurrent CDI.

Cohen noted that the number of prior recurrences in the participants was not provided, despite risk of recurrence increasing with the number of episodes. He also indicated he would have appreciated the study delving further than VRE colonization, to assess overall effect of the vancomycin on fecal microbiota.

Keating and colleagues acknowledged that the study had not evaluated broader effects of the oral vancomycin on the gut microbiome, despite known effects including reduction of baseline commensals which may facilitate C. difficile to recolonize.

"Additional research on patient populations, dosages, and dosing schedules may be needed to determine whether oral vancomycin may provide a greater protective effect within specific parameters while maintaining a low risk profile for patients," they remarked.

References
1. Keating JA, Xu T, Graham MB, et al. Oral vancomycin for prevention of recurrent Clostridioides difficile infection: A randomized clinical trial. JAMA Ntw Open. 2025; 8(7):e2517834.doi:10.1001/jamanetworkopen.2025.17834.
2. Cohen SH. Uncertain benefits of oral vancomycin for prevention of recurrent Clostridioides difficile infection. JAMA Ntw Open. 2025; 8(7):e2521084. doi:10.1001/jamanetworkopen.2025.21084.

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