The emergence of resistance to the fluoroquinolone (FQ) antibiotics is an issue of great concern at both the clinical and public health level. FQ resistance is particularly worrisome for Escherichia coli, the most common gram-negativebacterial pathogen. The emergence of FQ-resistant E. coli (FQR-EC) is of exceptional concern for long-term care facilities (LTCFs), because FQs, as the only oral antibiotic class with broad spectrum activity against gram-negative pathogens, are uniquely useful in treating infections in LTCF residents that would otherwise require hospitalization. Investigating FQR-EC in the LTCF setting is critical given the expected exponential future growth of the LTCF population, their high degree of debilitation with resultant high risk of poor outcomes due to infection, and the fact that LTCF residents, because of frequent visits to acute care facilities, may serve to introduce and disseminate FQR-EC to other healthcare settings. Despite these concerns, risk factors for FQR-EC in the LTCF have not been studied. While risk factors for FQR-EC have been identified in hospitalized patients, extrapolating these results to the LTCF is problematic because of the unique characteristics of the LTCF setting and its residents. Developing effective approaches to limit emergence of FQR-EC in the LTCF requires elucidation of the complex nature of the epidemiology of FQ resistance. Based on existing in vitro and clinical data, 1 may conceptualize 3 stages in the biological evolution of FQR-EC in an individual: 1) acquisition of new FQR-EC fecal colonization; 2) persistence of FQR-EC fecal colonization; and 3) progression to clinical FQR-EC infection. The primary reason to conceptualize these different stages is to increase the sensitivity in identifying critical components of the pathway that can be interrupted or manipulated clinically. To identify novel future interventions, the potential role of clinical risk factors (e.g., antibiotic use), transmission (e.g., exogenous acquisition of FQR-EC), and isolate characteristics (e.g., FQ resistance mechanism, virulence factor profile) must be considered at each of these stages in the evolution of FQR-EC. The primary aims of this study are: 1) to identify risk factors for new FQR-EC colonization in LTCF patients, 2) to identify risk factors for prolonged FQR-EC colonization in LTCF patients, and 3) to identify risk factors for clinical FQR-EC infection in FQR-EC colonized LTCF patients.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG023792-02
Application #
7077764
Study Section
Special Emphasis Panel (ZRG1-HOP-N (90))
Program Officer
Nayfield, Susan G
Project Start
2005-07-01
Project End
2010-06-30
Budget Start
2006-07-15
Budget End
2007-06-30
Support Year
2
Fiscal Year
2006
Total Cost
$551,324
Indirect Cost
Name
University of Pennsylvania
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
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