Tapered vancomycin dosing reduces CDI recurrence

Tapering the dose of vancomycin over 2 weeks following initial 14-day therapy appears to work better than the 14-day fixed dosing at reducing the recurrence of Clostridioides difficile infection (CDI), as shown in the TAPER-V trial.

Compared with patients who received vancomycin at 125 mg four times daily for 14 days (control), those who received tapered vancomycin doses for another 2 weeks had fewer CDI recurrences at day 56 (14.8 percent vs 17.7 percent; adjusted relative risk [RR], 0.84, 95 percent credible interval [CrI], 0.48–1.45), the primary outcome, reported lead investigator Dr Emily McDonald from the McGill University Health Centre Research Institute in Montreal, Canada. [ESCMID 2025, abstract L0023]

The percentage of patients with recurrent CDI at day 38 was also lower in the taper group than in the control group (6.7 percent vs 15.4 percent; adjusted RR, 0.43, 95 percent CrI, 0.19–0.89).

Tapered vancomycin dosing had a 74-percent probability of superiority compared with standard dosing at reducing recurrence at day 56. “What was really interesting was our key secondary outcome at day 38, which showed a 99-percent probability of superiority for the vancomycin taper group,” McDonald said.

In terms of other outcomes at day 90, none of the patients received a colectomy, and there were very few patients who went on to receive fidaxomicin (0.7 percent in the taper group vs 3.1 percent in the control group) as secondary therapy. Overall, 16.3 percent of patients in the taper group and 20.0 percent in the control group presented to the emergency department for CDI, and only 2.2 percent and 0.8 percent in the respective groups were hospitalized.

Subgroup analysis did not yield any particular subgroup for which the tapered vancomycin dosing was more or less favourable.

McDonald showed a Kaplan-Meier curve, which indicated a seemingly favourable initial effect of the 4-week tapered vancomycin dosing vs the 14-day standardized fixed dosing. She pointed out that the difference was quite pronounced at day 38, with the taper group showing a clear advantage. This separation appeared to persist through day 56, albeit less distinctly, before the curves nearly converged and overlapped around day 90.

Such pattern suggests that the vancomycin taper intervention is “potentially pushing out the recurrences, but effectively doing so,” she said.

Regarding safety, the side effects were very few, and the drug was well tolerated, McDonald noted. A total of 11.4 patients in the taper group and 10.1 percent in the control group experienced side effects, which led to treatment discontinuation in 1.5 percent and 2.3 percent, respectively. The most common adverse reactions were gastrointestinal in nature, including nausea (3.0 percent vs 0.8 percent), abdominal discomfort (2.3 percent vs 2.3 percent), and diarrhoea (1.5 percent vs 2.3 percent).

Overall, the findings from the TAPER-V trial hold clinical implications, as “options to prevent recurrence are expensive, not universally available, lack evidence, or removed from the market,” according to McDonald. On the other hand, “vancomycin is affordable, widely available, and has very few side effects.”

TAPER-V trial

TAPER-V included 265 adult patients (median age 63 years, 52.1 percent female) who tested positive for C. difficile and were undergoing vancomycin treatment for a first episode or first recurrence, enrolled from 16 hospitals across four Canadian provinces. Core exclusion criteria included failure to achieve clinical cure by the end of day 10, exclusive metronidazole treatment for more than 3 days, and receipt of fidaxomicin, faecal microbiota transplantation, or immunoglobulin products for the current episode.

Vancomycin treatment was standardized to 14 days at 125 mg four times daily. This meant that patients had to be taking vancomycin at that dosing schedule by the time they were enrolled in the study. At day 15 of treatment, the patients were randomly assigned to continue receiving vancomycin at a tapered dose for another 2 weeks (125 mg twice daily for 1 week, then once daily for 1 week; n=135) or to receive placebo capsules (n=130).

CDI recurrence was defined as at least three episodes of diarrhoea in 24 hours with a positive result on nucleic acid amplification test, toxin A/B enzyme immunoassay, or cell cytotoxicity assay. Patients who had <3 bowel movements could be included if they had a positive text result in the setting of ileus, toxic megacolon, or pseudomembranous colitis on colonoscopy.

TAPER-V had an adaptive design wherein interim analysis was planned at 125, 250, and 500 patients recruited. Bayesian binary regression was used, and prespecified statistical stopping rules for superiority (RR <1: 99 percent at 125, 97.5 percent at 250, and 97.5 percent at 500) and futility (<15 percent probability that the number needed to treat was <25) was applied.

“I think the verdict is pending when it comes to other comparisons. What would happen if we compared, for example, a vancomycin taper to fidaxomicin for first episodes and for subsequent recurrences? And then again, what would happen if we compared vancomycin taper to a fidaxomicin taper?” McDonald said.

“It would be really interesting to generate some randomized controlled trial data for fidaxomicin out to day 56 and day 90,” she added.