# Microbiologic impact of medical therapies for recurrent Clostridium difficile infection

> **NIH VA I01** · LOUIS STOKES CLEVELAND VA MEDICAL CENTER · 2021 · —

## Abstract

Approximately 25% of patients responding to treatment for initial cases of Clostridium difficile
infection (CDI) develop a recurrence of the infection, and many develop multiple recurrences.
Unfortunately, the optimal medical management of recurrent CDI is unclear. In particular,
vancomycin taper and pulse regimens are commonly used, but have not been compared to other
medical treatments in randomized trials. To address this deficiency, the VA Cooperative Studies
Program (CSP) is conducting a randomized trial, CSP596, to compare a standard 10-day course
of vancomycin versus 10 days of fidaxomicin versus 10 days of vancomycin followed by a
vancomycin taper and pulse regimen for first or second recurrences of CDI. We propose to
conduct a sub-study of the CSP trial to develop a better understanding of the microbiologic impact
of the treatment regimens. The central hypothesis of the proposal is that taper and pulse
treatment regimens facilitate clearance of spores from the colon while allowing recovery of
intestinal microbiota that provide colonization resistance to C. difficile. Our first specific aim is to
compare the composition of the indigenous intestinal microbiota and clearance of C. difficile in
patients receiving treatment with vancomycin taper and pulse regimens versus standard
vancomycin or fidaxomicin regimens for recurrent CDI. To accomplish this aim, we will collect
stool specimens before, during, and after treatment for a subset of 120 participants in the VA CSP
trial (~40 per treatment group). We will compare the composition of the microbiota and the
presence and concentration of C. difficile in stool of patients in each treatment group. Our second
specific aim is to determine if pulse dosing of vancomycin and fidaxomicin enhances clearance
of C. difficile spores. To accomplish this aim, we will use a mouse model of C. difficile colonization
to compare clearance of C. difficile spores and recovery of the microbiota with every 2 or 3-day
pulse dosing of vancomycin or fidaxomicin in comparison to daily dosing for the same treatment
duration and to the standard 10-day treatment regimens used in the CSP# 596 trial. The results
will be significant because recurrent CDI is an important clinical challenge and there is an urgent
need for effective management approaches.

## Key facts

- **NIH application ID:** 9872020
- **Project number:** 5I01CX001848-02
- **Recipient organization:** LOUIS STOKES CLEVELAND VA MEDICAL CENTER
- **Principal Investigator:** Curtis Donskey
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2021
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2019-04-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9872020

## Citation

> US National Institutes of Health, RePORTER application 9872020, Microbiologic impact of medical therapies for recurrent Clostridium difficile infection (5I01CX001848-02). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9872020. Licensed CC0.

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