University of Wisconsin–Madison–led researchers report lower yet statistically non-significant recurrence of Clostridioides difficile (C. diff) among adults given low-dose oral vancomycin during antibiotic therapy.

Antibiotics used in hospital settings can disrupt the normal gut flora. Although antibiotic resistance remains uncommon, C. diff spores can survive antibiotic courses and take over in the absence of competing microbiota. Once allowed to become dominant, C. diff is notoriously difficult to clear, frequently showing up again and again after treatments.

Previous investigations have found signals that vancomycin might be beneficial, but with confounding, variable inclusion criteria, and unclear results, something the current trial had hoped to avoid.

In the study, “Oral Vancomycin for Prevention of Recurrent Clostridioides difficile Infection,” published in JAMA Network Open, researchers conducted a Phase II, double-blind, placebo-controlled randomized clinical trial to evaluate whether once-daily 125 mg oral vancomycin can prevent recurrent infection.

Enrollment comprised 81 adults who had completed treatment for C. diff within the past 180 days and were initiating systemic antibiotics for non-C. diff indications, recruited between 2018 and mid 2023.

Participants were enrolled at four health systems: University of Wisconsin–Madison Health (55), Medical College of Wisconsin (18), Henry Ford Hospital (six), and Mayo Clinic (two).

Participants were randomized 1:1 to oral vancomycin or lactose placebo taken throughout the antibiotic course plus five additional days. Weekly telephone follow-ups captured symptoms, and stool testing employed two-step toxin assays for confirmed recurrences. Secondary analysis assessed vancomycin-resistant Enterococcus carriage from stool or perirectal swabs collected at baseline and week eight.

Recurrent C. diff emerged in 17 of 39 participants receiving vancomycin (43.6%) versus 24 of 42 receiving placebo (57.1%), an absolute difference of −13.5 percentage points (95% CI, −35.1% to 8.0%; P = .22). Adverse events affected 27 participants in each group, primarily gastrointestinal disorders. Eight-week gut colonization by vancomycin-resistant Enterococcus was detected in 15 of 30 vancomycin recipients (50.0%) and six of 25 placebo recipients (24.0%; P = .048).

Investigators originally calculated that roughly 150 participants would be needed to give the trial 80% power to detect a 20-percentage-point drop in C. diff recurrence. Recruitment stalled at 81. Nearly 40% of otherwise-eligible patients declined because they were already taking prophylactic vancomycin and would not risk placebo, and a pandemic-related suspension of research visits further slowed accrual.

With just over half the planned sample, confidence intervals around the primary outcome were wide (–35.1 to 8.0 percentage points) and the P value rose to .22, leaving chance as a plausible explanation for the observed 13.5-point difference. Authors therefore state that the study was underpowered, unable to confirm or refute oral vancomycin‘s preventive effect.

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