Clostridium difficile infection as a result of antibiotic exposure is the most common cause of nosocomial diarrhea. Residents of long-term care facilities (LTCFs) are particularly vulnerable due to their inherent frailty and frequent receipt of antibiotics. Besides treating infections, antibiotics also disrupt commensal bacteria within the intestine. These bacteria, collectively called the human gut microbiome, help protect against enteric pathogens through colonization resistance. The goal of this application is to identify bacterial taxa that permit the human gut microbiota to maintain colonization resistance against C. difficile. The central hypothesis is that colonization resistance established by older adults'gut microbiota has delayed recovery following antibiotic exposure, rendering this population more vulnerable to C. difficile infection.
The specific aims are as follows: 1. Determine the host and antibiotic factors associated with delayed recovery of microbial genetic diversity among LTCF residents who receive systemic antibiotics. Stool samples will be collected from LTCF residents as they complete antibiotics and then for an additional 8-12 weeks. Denaturing gradient gel electrophoresis (DGGE) will be used to follow changes in the gut microbiota. Specifically, the time between completing antibiotics and recovering a stable gut microbiome, as well as the genetic diversity of that microbiome, will be determined. The influence of other factors, including host comorbidities, the number of antibiotics administered and the total days of antibiotic therapy, will be examined. 2. Determine the bacterial taxa involved with restoration of colonization resistance. Using the same cohort from Aim 1, stool samples will be tested for prevention of C. difficile overgrowth in vitro, a functional test of colonization resistance. Subsequently, 16S rRNA pyrosequencing will be used to compare changes in bacterial taxa before and after restoration of colonization resistance. Understanding the effect of systemic antibiotics on the human gut microbiota of LTCF residents and factors related to robust recovery of gut bacteria will help improve antibiotic utilization. This knowledge, in turn, will support the development of an evidence-based antibiotic stewardship program designed to reduce the prevalence of C. difficile infection among LTCF residents.

Public Health Relevance

The intestine is home to a myriad of commensal bacteria that help protect humans from pathogens such as Clostridium difficile, which causes infectious diarrhea among people who have received antibiotics. Residents of long-term care facilities, who frequently receive antibiotics, are particularly vulnerable to C. difficile infection. The goal of this application is to understand which groups of intestinal bacteria protect humans from C. difficile infection. To do this, we will examine changes in the intestinal bacteria of long-term care facility residents as they recover from antibiotic exposure, seeking to identify those factors related to robust recovery of gut bacteria.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Small Research Grants (R03)
Project #
5R03AG040722-02
Application #
8323227
Study Section
Special Emphasis Panel (ZAG1-ZIJ-9 (M1))
Program Officer
Salive, Marcel
Project Start
2011-09-01
Project End
2013-08-31
Budget Start
2012-09-01
Budget End
2013-08-31
Support Year
2
Fiscal Year
2012
Total Cost
$63,000
Indirect Cost
$13,000
Name
Case Western Reserve University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
077758407
City
Cleveland
State
OH
Country
United States
Zip Code
44106