# Initial Vancomycin Taper for the Prevention of Recurrent Clostridioides difficile Infection: A Randomized Clinical Trial

## TL;DR

A 4-week vancomycin pulse and taper regimen may help prevent early recurrence of Clostridioides difficile infection compared to a 2-week pulse regimen.

## Contribution

The study introduces a new vancomycin taper regimen to reduce recurrence of Clostridioides difficile infection.

## Key findings

- The vancomycin pulse and taper regimen had a 73.8% posterior probability of superiority in preventing recurrence at day 56.
- Recurrence at day 38 was significantly lower in the taper group compared to the pulse-only group.
- Adverse effects were rare in both treatment groups.

## Abstract

Does a 4-week pulse and taper regimen of vancomycin reduce the risk of recurrent Clostridioides difficile infection compared with a standard pulse regimen among patients with a first episode or first recurrence?

In this randomized clinical trial of 265 participants, the posterior probability of superiority for vancomycin pulse plus taper was 74%. The trial was stopped early due to feasibility of recruitment.

The vancomycin pulse and taper regimen could represent a safe and accessible treatment option to delay or prevent early recurrence of C difficile infection.

This randomized clinical trial tested whether a 4-week pulse and taper vancomycin regimen was superior to a 2-week pulse regimen for preventing recurrence among patients with a first episode or first recurrence of Clostridioides difficile infection.

Clostridioides difficile infection (CDI) is associated with substantial morbidity and mortality, and recurrent CDI (rCDI) is common.

To determine whether a 4-week vancomycin pulse and taper regimen would be superior to a standard 2-week vancomycin pulse regimen in terms of recurrence.

This parallel-design, double-blind clinical trial was performed at 12 Canadian hospitals. Adults with a first episode or first recurrence of CDI were eligible to participate. Patients needed to have clinical CDI with laboratory confirmation and to have improved by day 10 of treatment. Recruitment began November 19, 2020, and all follow-up was completed by October 4, 2024.

All patients received a 2-week pulse of vancomycin (standardized at 125 mg orally 4 times a day at the time of recruitment) and were then randomized to receive either vancomycin taper (125 mg orally twice a day for 7 days and then 125 mg once a day for 7 days) or an equivalent schedule of placebo capsules.

The primary outcome was the posterior probability of superiority of the vancomycin pulse and taper regimen to prevent rCDI at day 56. A secondary outcome was recurrence at day 38. Binary outcomes were analyzed using a bayesian generalized linear model with minimally informative priors yielding log relative risk (RR) with 95% bayesian credible intervals (CrIs).

The trial was stopped early due to feasibility of recruitment. Among 265 participants (135 in the intervention group and 130 in the control group; median age, 63 [IQR 47-74] years; 138 [52.1%] women), recurrence at day 56 occurred in 20 of 135 patients (14.8%) in the vancomycin pulse and taper group compared with 23 of 130 (17.7%) in the vancomycin pulse group (adjusted RR, 0.84 [95% CrI, 0.48-1.45]; posterior probability of superiority, 73.8%). Recurrence at day 38 occurred in 9 of 135 patients (6.7%) in the vancomycin pulse and taper group compared with 20 of 130 (15.4%) in the vancomycin pulse group (adjusted RR, 0.43 [95% CrI, 0.19-0.89]; posterior probability of superiority, 99.0%). Adverse effects were rare in both groups.

In this randomized clinical trial, a 4-week vancomycin pulse and taper regimen had a probability of 73.8% to be superior to a 2-week pulse regimen. This approach may represent a safe and accessible treatment option to delay or prevent early CDI recurrence.

ClinicalTrials.gov Identifier: NCT04138706