Clostridium difficile is a major pathogen causing serious healthcare-associated infection. Compared with younger adults, adults 60 years of age and older have an increased incidence of Clostridium difficile infection (CDI) and are far more likely to suffer adverse consequences of CDI such as prolonged diarrhea symptoms, reduced functional ability, recurrence, mortality and prolonged hospitalization. Thus, our proposed area of study, CDI is directly relevant to the healthcare needs and quality of life of older adults. However, therapeutic options for CDI are limited. We propose a pilot feasibility clinical trial in subjects receiving care at the University of Wisconsin Hospital and Clinics Madison, WI to evaluate the use of a biotherapeutic agent, Lactobacillus rhamnosus HN001, as an adjunct to antibiotic treatment to reduce the duration of diarrhea in hospitalized patients with a first episoe of CDI. We have two hypotheses: (1) The probiotic L. rhamnosus HN001, when compared with placebo, will reduce the duration of diarrhea in patients with CDI (2) The probiotic L. rhamnosus HN001, when compared with placebo, will reduce CDI recurrence, fecal lactoferrin levels, and quantity of C. difficile toxin while improving functional status. To investigate these hypotheses, we are proposing the following specific aims:
SPECIFIC AIM 1 : To determine the efficacy of adjunctive probiotic use during a first episode of CDI to reduce the duration of diarrhea in patients with CDI compared to standard of care and placebo SPECIFIC AIM 2: To determine the efficacy of adjunctive probiotic use during a first episode of CDI to reduce CDI recurrence compared to standard of care and placebo SPECIFIC AIM 3 (Exploratory): To determine the effect of adjunctive probiotic use during a first episode of CDI on density of C. difficile toxin i stool, stool cytokines, fecal lactoferrin and functional status. Our study population includes hospitalized patients at the University of Wisconsin Hospital and Clinics who have a first episode of CDI. Potential subjects will be identified by reviewing microbiology lists of patients with CDI. Subjects with CDI will be randomized to probiotic or placebo for 4 weeks in addition to usual antibiotic treatment of CDI according to standard of care. Duration of followup is 8 weeks. Stool specimens will be collected at baseline, 4 weeks and 8 weeks. The primary outcome is duration of diarrhea. Data collection will occur by use of stool diaries, stool sample collection and electronic chart review. Adherence will be encouraged by weekly phone calls. The study will provide important preliminary pilot data for a subsequent larger study to examine the efficacy of probiotics for CDI. If found to be efficacious and feasible in the older adult population, probiotis represent an easily implementable, safe, and well-tolerated intervention that may prove a useful adjunctive treatment for CDI.

Public Health Relevance

Clostridium difficile is a major pathogen causing serious infections in older adults. Current treatment with antibiotics do not consistently improve diarrhea symptoms or reduce the risk of recurrence. The alternative being tested by the work proposed involves treatment with a probiotic or live microorganism. If this non-antibiotic-based treatment in addition to antibiotics reduces the duration of diarrhea in older adults with Clostridium difficle infection (CDI), it will represent a low-cost, easily implementable option for reducing the adverse consequences of CDI in older adults.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Small Research Grants (R03)
Project #
1R03AG040669-01A1
Application #
8339985
Study Section
Special Emphasis Panel (ZAG1-ZIJ-9 (M1))
Program Officer
Salive, Marcel
Project Start
2012-08-01
Project End
2014-07-31
Budget Start
2012-08-01
Budget End
2013-07-31
Support Year
1
Fiscal Year
2012
Total Cost
$75,250
Indirect Cost
$25,250
Name
University of Wisconsin Madison
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
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