Vancomycin Taper Strategies to Prevent C Difficile Recurrence, With Emily McDonald, MD, MSc

Recurrent infection is widely regarded as one of the most frustrating and costly challenges in the management of Clostridioides difficile infection (CDI), which affects an estimated 450,000 patients annually in the United States and carries substantial morbidity and healthcare costs.

For many patients, the illness does not end after the first episode. According to the US Centers for Disease Control and Prevention, about 1 in 9 people who get CDI will get it again in the subsequent 2-8 weeks.

"It's very unpleasant, can be quite morbid for patients, and once you've had a C difficile infection, unfortunately, there's a risk that it can come back over and over again,” Emily McDonald, MD, MSc, an associate professor of medicine at McGill University, explained to HCPLive. “You can imagine how that can be pretty traumatic for patients, difficult to manage, and costly to the healthcare system, so it remains a big problem.”

Her new research published in JAMA Network Open explored a potential strategy to reduce these recurrences: using an initial vancomycin taper regimen after standard therapy. Results suggest a 4-week vancomycin pulse and taper regimen may offer a safe and accessible treatment option to delay or prevent early CDI recurrence.

McDonald and colleagues performed the parallel-design, double-blind clinical trial at 12 hospitals in Canada and enrolled adults with a first episode or first recurrence of CDI. For inclusion, patients were required to have clinical CDI with laboratory confirmation and to have improved by day 10 of treatment.

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 random;ly assigned 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 (n = 135 in the intervention group; n = 130 in the control group), recurrence at day 56 occurred in 14.8% of the vancomycin pulse and taper group compared with 17.7% of 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 6.7% of the vancomycin pulse and taper group compared with 15.4% of the vancomycin pulse group (adjusted RR, 0.43; 95% CrI, 0.19-0.89; posterior probability of superiority, 99.0%).

McDonald noted that findings have important implications in a treatment landscape that increasingly includes fidaxomicin, a guideline-preferred therapy that has demonstrated lower recurrence rates than vancomycin in prior studies. However, fidaxomicin remains significantly more expensive and less accessible in many healthcare systems.

According to McDonald, the results suggest that if clinicians are already planning to use vancomycin, extending therapy with a taper may be a practical strategy to reduce early recurrence risk. However, whether the taper approach ultimately proves comparable to fidaxomicin over longer follow-up remains an open question.

“I think it depends on what you have available, what the patient can afford, and your healthcare system,” McDonald said. “If you're using vancomycin, I would use the taper. I think it's a reasonable option compared to fidaxomicin, but that's a hypothesis. We don't know the answer for day 56.”

Editors’ Note: McDonald reports relevant disclosures with Fond de Recherche Sante Quebec.

References

1. McDonald EG, Butler-Laporte G, Brophy JM, et al. Initial Vancomycin Taper for the Prevention of Recurrent Clostridioides difficile Infection: A Randomized Clinical Trial. JAMA Netw Open. 2026;9(2):e2560495. doi:10.1001/jamanetworkopen.2025.60495

2. US Centers for Disease Control and Prevention. After C. diff: Caring for Yourself and Others. December 13, 2024. Accessed March 16, 2026. https://www.cdc.gov/c-diff/after/index.html